InTechOpen uses cookies to offer you the best online experience. By continuing to use our site, you agree to our Privacy Policy.

Neuroscience » "The Amygdala - A Discrete Multitasking Manager", book edited by Barbara Ferry, ISBN 978-953-51-0908-2, Published: December 19, 2012 under CC BY 3.0 license. © The Author(s).

Chapter 15

Amygdala in Alzheimer's Disease

By Shira Knafo
DOI: 10.5772/52804

Article top


Coronal sections through the amygdala and adjacent regions showing the pattern of distribution of amyloid plaques.
Figure 1. Coronal sections through the amygdala and adjacent regions showing the pattern of distribution of amyloid plaques.
Intracellular injections
Figure 2. Intracellular injections

Amygdala in Alzheimer's Disease

Shira Knafo

1. Introduction

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes debilitating dementia. For yet unknown reason, AD often leads also to emotional instability. Neuropathologically, AD brains are characterized by the presence of extracellular fibrillar amyloid beta peptide (Aβ) in amyloid plaques, intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated tau, and elevated brain levels of soluble Aβ oligomers. Plaques and neurofibrillary tangles are observed mostly in the cerebral cortex, but subcortical regions such as nucleus basalis, thalamus, locus coeruleus and raphe nuclei are also affected (Price et al., 1991). The amygdala is another important subcortical region that is severely and consistently affected by pathology in AD. This chapter will discuss the neuropathological features of the amygdala affected by AD and the resulting psychological, emotional and cognitive disturbances in AD patients and in model mice of this disease.

2. Emotional disturbances in AD patients

The amygdala is part of the limbic system that plays a major role in the processing and memorizing of emotional reactions (Schafe et al., 2005). The involvement of the amygdala in emotion has been evidenced in monkeys by the overwhelming loss of normal social and affective behavior resulting from bilateral damage to this structure (Izquierdo et al., 2005; Izquierdo and Murray, 2007). The amygdala is affected early in AD and results by neuropsychiatric symptoms leading to functional deficits that greatly contribute to the disability associated with this disease. Due to the early damage to the amygdala, neuropsychiatric symptoms are very common in mild stages of AD. Eventually, approximately 80% of the patients with AD present neuropsychiatric symptoms, such as hallucinations, delusions, paranoia, anxiety, agitation, and affective disturbances during the course of their illness (Mega et al., 1996; Lyketsos et al., 2002). Other symptoms such as dysphoria, irritability, disinhibition and apathy are also common (Kaufer et al., 1998). In addition to these symptoms, AD patients frequently show personality changes that affect their activities of daily living and the interaction with their caregivers. Personality changes may appear in any phase of dementia but often precede other early clinical manifestations of the disease, such as cognitive impairment and mood changes. These changes may therefore help in the clinical diagnosis of AD at early stages (Robins Wahlin and Byrne, 2011). Interestingly, personality changes and some of the neuropsychiatric symptoms (agitation, dysphoria and apathy) are better correlated with the severity of cognitive, functional and behavioral signs than with the patient’s age, gender, education or disease duration (Mega et al., 1996; Talassi et al., 2007). Thus, personality changes and neuropsychiatric symptoms may reflect the impact of progressive brain damage in AD (Robins Wahlin and Byrne, 2011).

3. Emotional memory in AD

Emotional memory is a form of episodic memory defined as memory of arousing emotional events. These memories are sometimes referred to as "flashbulb" memories (Hamann et al., 2000). Results from studies in animals and humans have strongly implicated the amygdala in this memory type (LaBar, 2003; Brierley et al., 2004; Richter-Levin, 2004). While it is recognized that normal people better remember events associated with an emotional component, there is a controversy regarding the strength of emotional memory in AD patients (Satler et al., 2007; Schultz et al., 2009; Huijbers et al., 2011; Nashiro and Mather, 2011; Sundstrom, 2011). Since the amygdala is one of the structures damaged in early stages of the AD pathology, it has been hypothesized that emotional memory should be impaired in AD patients. Indeed, data have shown that unlike healthy individuals, AD patients do not show memory enhancement for emotional events (enhanced memory for emotional compared to neutral stimuli) in spite of normal emotional reactions (Hamann et al., 2000). Notably, the degree of emotional memory impairment has positively been correlated with the extent of the amygdaloid atrophy (Mori et al., 1999a, b; Fleming et al., 2003).

4. Pathology of the amygdala in AD patients

While normal aging primarily affects the prefrontal cortex but relatively spares limbic regions, AD mainly affects limbic regions. The amygdala of AD patients shows a considerable shrinkage, distortion and loss of neurons, and widespread gliosis (Vereecken et al.; Herzog and Kemper, 1980; Cuenod et al., 1993). The amygdaloid atrophy in AD is the result of neuronal death (especially in the magnocellular basolateral amygdalar nuclei group) and loss of dendrites and axons. The accumulation of intraneuronal neurofibrillary tangles, Lewy bodies and extracellular Amyloid β peptide (Aβ) deposits in plaques also contribute significantly to the atrophy. Detailed pathological examination of the amygdala of AD patients reveals that many neurofibrillary tangles and Aβ plaques are located in the accessory basal and cortical nuclei and in the cortical transition area, whereas the mediobasal nucleus is less affected (Kromer Vogt et al., 1990). The medial, lateral, laterobasal and central nuclei are relatively free of neurofibrillary tangles and Aβ plaques (Kromer Vogt et al., 1990). Interestingly, it has been observed that the morphological deformation of the amygdala in AD patients is associated with intrinsic damage to its subnuclei and their reciprocal connectivity with other brain areas. Specifically, it has been reported that amygdaloid nuclei receiving input from and giving rise to hippocampal projections are consistently affected by neuropathological alterations in AD. In contrast, amygdaloid nuclei which receive strong cholinergic input from nucleus basalis of Meynert (e.g. laterobasal nucleus) are less affected (Kromer Vogt et al., 1990). To conclude, histological analysis of the amygdala of AD patients allows a thorough examination of this region thus rendering possible to detect nucleus-specific pathologies. Nevertheless, the major limitation of post-mortem analysis is that it is typically performed on brains taken from patients at late stages of the disease. Thus, information is lacking regarding neuropathological alterations in early stages of AD.

5. Imaging of the amygdala in vivo

Whereas histological procedures are used to investigate the anatomical complexity of the amygdala in brains from AD patients, a standard magnetic resonance imaging (MRI) technique can only detect few internal details and similar resolution cannot be obtained. The discovery that neuronal loss is a cause of amygdaloid atrophy provided the basis for later studies correlating amygdaloid volumetry, as measured with MRI, with the cognitive status of individual AD patients. Indeed, MRI-based volumetry is now regularly used as a research tool to explore the relationship between amygdaloid volume and the onset and progression of AD (de Leon et al., 1996; Mori et al., 1999a; Vasconcelos et al., 2011). While in the past the use of MRI was limited to clinical studies, the recent rise in MRI accessibility allowed its utilization for non-clinical studies aimed at investigating the involvement of the amygdala in emotion, memory processes and personality (Mori et al., 1999a). The main disadvantage of MRI-based amygdaloid volumetry consists in the difficulty to precisely and reliably delineate the contours of the amygdala in vivo. This difficulty arises from the similarity in MRI signal intensities between the amygdala and other temporal lobe structures surrounding it (hippocampus proper, subiculum, entorhinal cortex, claustrum and tail of the caudate)(Convit et al., 1999). Nevertheless, new imaging techniques such as ultrahigh field structural MRI enable clear in vivo detection and even segmentation of the amygdala (Solano-Castiella et al., 2011), and might be used to investigate the anatomical features of different amygdaloid nuclei in AD patients.

Numerous studies measuring the amygdaloid volume (normalized to intracranial volume) in AD patients at different clinical stages and in healthy age-matched controls showed a correlation of this factor with the neuropsychological performance of each patient. These studies have consistently demonstrated a decrease in amygdaloid volume in AD patients when compared to healthy controls (Horinek et al., 2007; Beacher et al., 2009; Cherubini et al., 2010; Lehmann et al., 2010; Vasconcelos Lde et al., 2011). Importantly, atrophy of the amygdala was found even in preclinical stages of the disease (Fox et al., 1996; Heun et al., 1997; Golebiowski et al., 1999). In fact, in the very early stages of AD, amygdaloid volume reductions were at least as large as hippocampal volume reductions although at this stage some overlap does exist between patients and healthy controls. Still, the volume of the amygdala has been suggested to be an independent variable in predicting conversion from mild cognitive impairment to AD (Liu et al., 2010).

Functional MRI. Increasing number of neuroimaging studies using functional MRI (fMRI) are used to examine the neuronal activity of the amygdala by detecting changes in local blood perfusion, blood volume or blood oxygenation. Injecting contrast agents are often used in this technique. In some studies, voxel-based morphometry (VBM) on MRI was combined with Positron Emission Tomography (PET) to compare activity in specific brain areas in AD patients and healthy controls (Kawachi et al., 2006). Functional MRI studies showed that the amygdala is excessively responsive to human faces (both novel emotional and familiar neutral expressions) in mild AD patients relative to elderly controls (Wright et al., 2007). On the other hand, AD patients presented deficits in the recognition of some facial expressions of emotion (happy, sad, fearful, and neutral expressions)(Kohler et al., 2005). These alterations in the normal activity of the amygdala probably contribute to the significant social and behavioral defects observed in AD patients.

Positron Emission Tomography (PET). PET is almost exclusively used to image the brain, and may be used to detect functional abnormalities early in the course of AD, way before anatomical changes occur. For example, PET was used to examine acetylcholine esterase activity in vivo in the amygdala and cerebral cortex (Shinotoh et al., 2003). To note, levels of acetylcholine are significantly decreased in AD due to degeneration of the cholinergic magnocellular neurons of the nucleus basalis of Meynert (nbM) that send cholinergic projection mainly to the amygdala (Mesulam, 2004). In fact, the degree of the cholinergic loss is positively correlated with the severity of dementia in AD (Perry et al., 1981), probably due to the importance of nbM in emotional memory consolidation. PET measurements of C-11-labeled N-methyl-4-piperidyl-acetate (MP4A, a specific substrate of AChE) have shown that AChE activity is significantly reduced in patients with AD in both the amygdala and cerebral cortex (Shinotoh et al., 2003). Importantly, these deficits are present in mild to moderate AD, supporting the notion that cortical and amygdaloid functional changes of the cholinergic system occur early in AD (Herholz et al., 2004). These functional alterations are therefore suggested to serve as a physiologic and noninvasive marker for certain neuropsychiatric manifestations of mild AD. In addition, these finding suggest that the amygdala should receive an important attention in studies of the mild or even prodromal stages of AD (Basso et al., 2006) even though considerable evidences continue to support the focus on the hippocampus in MRI studies of AD.

6. The use of AD mice model to study the Aβ-dependent changes in the amygdala

In modern AD research, transgenic mice bearing infrequent mutations leading to familial forms of AD are being used to characterize in details the physiological, morphological and behavioral consequences of AD neuropathology in order to understand the anatomical and synaptic basis of dementia (Selkoe, 1996). These mutations include mutations in amyloid precursor protein (APP), the precursor of the Aβ peptide, or in presenilin (PS) 1 or 2, the catalytic subunit of the gamma secretase complex, which cleaves APP to form Aβ. Transgenic AD mice model represents an important tool to examine the consequences of in vivo Aβ accumulation and were proved to mimic many of the pathological features of AD (Spires and Hyman, 2005; Spires-Jones and Knafo, 2012). APP and APP/PS1 mice present abundant extracellular Aβ plaques, synaptic dysfunction and loss, astrocytosis, activation of microglia and cognitive deficits (Games et al., 1995). The fact that Aβ plaques occupy a minor fraction (less than 5%) of the neuropil (see Fig. 1) in cognitively impaired transgenic mice (Knafo et al., 2009; Merino-Serrais et al., 2011) and the lack of correlation between the plaque load and the degree of cognitive impairment in AD patients (Terry et al., 1991; Terry, 2000), support the notion that fibrillar Aβ in plaques does not contribute significantly to dementia in AD patients. Instead, soluble Aβ assemblies (i.e. oligomeric or protofibrillary Aβ species that linger in aqueous solution after high-speed centrifugation) seem to be the main factors responsible for the structural, synaptic and cognitive deficits in these mice and probably also in initiating disease in AD patients (Selkoe, 2002).


A section stained with the anti-Aβ antibody and Nissl.BLA = basolateral nucleus of the amygdala; EC = external capsule; LA = lateral nucleus of the amygdala; PIR = piriform cortex. Scale bar, 350 μm (Knafo et al., 2009)

Figure 1.

Coronal sections through the amygdala and adjacent regions showing the pattern of distribution of amyloid plaques.

In a recent study, transgenic mice expressing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) (APP/PS1, Borchelt et al., 1997) were used to study the morphological basis for amygdala-dependent cognitive impairment (Knafo et al., 2009). In this study, the authors first showed a clear impairment of auditory fear conditioning in APP/PS1 mice, a learning task that depends on the lateral nucleus of the amygdala (LA) (Knafo et al., 2009). Importantly, this cognitive deficit did not result from changes in anxiety or sensitivity to shock. Then, the authors used intracellular injection of Alexa594 into projection neurons in the LA, combined with thioflavin-S plaque staining (Fig. 2) and three-dimensional reconstructions of the dendritic trees and spines. The results of this study show that in APP/PS1 mice the morphology of projection neurons in the amygdala is modified, as reflected by changes in dendritic complexity, and that there is a


(a) Panoramic confocal (10×) views of the lateral amygdala showing Alexa594-injected neurons and thioflavin-s-positive plaques in a Tg- mouse (left) and an APP/PS1 mouse (right). (b) Representative images of projection neurons from a Tg- mouse (left) and an APP/PS1 mouse (right). (c) The method used to distinguish dendrites and spines within and outside plaques. Left: a plaque suspected of containing a dendrite due to the rotation of its three-dimensional image. Center: the plaque surface is marked with the aid of the IsoSurface tool of Imaris software. Right: the voxels outside the surface are set to zero, leaving only the dendritic segment within the plaque (Knafo et al., 2009).

Figure 2.

Intracellular injections

significant decrease in number of large spines on these neurons (Knafo et al., 2009). The authors emphasized the finding that the morphological alteration in dendrites and spines occur mainly in plaque-free areas that occupy most of the neuropil. Thus, as spines are main postsynaptic elements of excitatory synapses in the brain (Gray, 1959) and are fundamental in memory, learning and cognition (Lamprecht and LeDoux, 2004) the authors suggested that these changes, rather than changes detected within plaques contribute to the cognitive impairment seen in APP/PS1 mice.

To summarize, amygdala is significantly and consistently affected by Aβ both in patients with AD and in mouse models of this disease. Therefore, this region is a central participant in the pathology of AD (Unger et al., 1991) and its damage may be the structural substrate to the frequent emotional, psychological, and memory disturbances seen in this devastating disorder.


1 - M Basso, J Yang, L Warren, MacAvoy MG, Varma P, Bronen RA, van Dyck CH (2006Volumetry of amygdala and hippocampus and memory performance in Alzheimer’s diseasePsychiatry Research: Neuroimaging146251261
2 - F Beacher, E Daly, A Simmons, V Prasher, R Morris, C Robinson, S Lovestone, K Murphy, D. G Murphy, 2009Alzheimer’s disease and Down’s syndrome: an in vivo MRI study. Psychological medicine 39675684
3 - D. R Borchelt, T Ratovitski, J Van Lare, M. K Lee, V Gonzales, N. A Jenkins, N. G Copeland, D. L Price, S. S Sisodia, 1997Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins.Neuron19939945
4 - B Brierley, N Medford, P Shaw, A. S David, 2004Emotional memory and perception in temporal lobectomy patients with amygdala damageJournal of neurology, neurosurgery, and psychiatry 75593599
5 - A Cherubini, P Peran, I Spoletini, Di Paola M, Di Iulio F, Hagberg GE, Sancesario G, Gianni W, Bossu P, Caltagirone C, Sabatini U, Spalletta G (2010Combined volumetry and DTI in subcortical structures of mild cognitive impairment and Alzheimer’s disease patients. J Alzheimers Dis 1912731282
6 - A Convit, P Mchugh, O. T Wolf, M. J De Leon, M Bobinski, S De Santi, A Roche, W Tsui, 1999MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation. Psychiatry Res 90113123
7 - C-A Cuenod, A Denys, J-L Michot, P Jehenson, F Forette, D Kaplan, A Syrota, F Boller, 1993Amygdala Atrophy in Alzheimer’s Disease: An In Vivo Magnetic Resonance Imaging Study. In, 941945
8 - M. J De Leon, A Convit, A. E George, J Golomb, S De Santi, C Tarshish, H Rusinek, M Bobinski, C Ince, D Miller, H Wisniewski, 1996In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer’s disease.Annals of the New York Academy of Sciences777113
9 - K Fleming, S. H Kim, M Doo, G Maguire, S. G Potkin, 2003Memory for emotional stimuli in patients with Alzheimer’s diseaseAm J Alzheimers Dis Other Demen 18340342
10 - N. C Fox, E. K Warrington, P. A Freeborough, P Hartikainen, A. M Kennedy, J. M Stevens, M. N Rossor, 1996Presymptomatic hippocampal atrophy in Alzheimer’s disease. A longitudinal MRI study.Brain 119 ( Pt 6):2001 EOF7 EOF
11 - D Games, et al1995Alzheimer-type neuropathology in transgenic mice overexpressing 717Fbeta]-amyloid precursor protein. Nature523 EOF7 EOF
12 - M Golebiowski, M Barcikowska, A Pfeffer, 1999Magnetic resonance imaging-based hippocampal volumetry in patients with dementia of the Alzheimer typeDement Geriatr Cogn Disord 10284288
13 - E. G Gray, 1959Electron microscopy of synaptic contacts on dendrite spines of the cerebral cortex.Nature18315921593
14 - S. B Hamann, E. S Monarch, F. C Goldstein, 2000Memory enhancement for emotional stimuli is impaired in early Alzheimer’s disease.Neuropsychology148292
15 - K Herholz, S Weisenbach, G Zandorf, O Lenz, H Schröder, B Bauer, E Kalbe, W. D Heiss, 2004In vivo study of acetylcholine esterase in basal forebrain, amygdala, and cortex in mild to moderate Alzheimer disease.Neuroimage21136143
16 - A. G Herzog, T. L Kemper, 1980Amygdaloid Changes in Aging and Dementia.In, 625629
17 - R Heun, M Mazanek, K. R Atzor, J Tintera, J Gawehn, M Burkart, M Gansicke, P Falkai, P Stoeter, 1997Amygdala-hippocampal atrophy and memory performance in dementia of Alzheimer type. Dement Geriatr Cogn Disord 8329336
18 - D Horinek, A Varjassyova, J Hort, 2007Magnetic resonance analysis of amygdalar volume in Alzheimer’s disease.Current opinion in psychiatry20273277
19 - M. J Huijbers, H. C Bergmann, Olde Rikkert MG, Kessels RP (2011Memory for emotional pictures in patients with Alzheimer’s dementia: comparing picture-location binding and subsequent recognitionJournal of aging research 2011:409364.
20 - A Izquierdo, E. A Murray, 2007Selective Bilateral Amygdala Lesions in Rhesus Monkeys Fail to Disrupt Object Reversal Learning.The Journal of Neuroscience 2710541062
21 - A Izquierdo, R. K Suda, E. A Murray, 2005Comparison of the Effects of Bilateral Orbital Prefrontal Cortex Lesions and Amygdala Lesions on Emotional Responses in Rhesus Monkeys.The Journal of Neuroscience 2585348542
22 - D. I Kaufer, J. L Cummings, D Christine, T Bray, S Castellon, D Masterman, MacMillan A, Ketchel P, DeKosky ST (1998Assessing the impact of neuropsychiatric symptoms in Alzheimer’s disease: the Neuropsychiatric Inventory Caregiver Distress Scale.Journal of the American Geriatrics Society46210215
23 - T Kawachi, K Ishii, S Sakamoto, M Sasaki, T Mori, F Yamashita, H Matsuda, E Mori, 2006Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer’s diseaseEuropean journal of nuclear medicine and molecular imaging33801809
24 - S Knafo, C Venero, P Merino-serrais, I Fernaud-espinosa, J Gonzalez-soriano, I Ferrer, G Santpere, J Defelipe, 2009Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer’s disease. The Journal of pathology 2194151
25 - C. G Kohler, G Anselmo-gallagher, W Bilker, J Karlawish, R. E Gur, C. M Clark, 2005Emotion-Discrimination Deficits in Mild Alzheimer DiseaseAmerican Journal of Geriatric Psych 13926933
26 - Kromer Vogt LJHyman BT, Van Hoesen GW, Damasio AR (1990Pathological alterations in the amygdala in Alzheimer’s disease.Neuroscience37377385
27 - LaBar KS (2003Emotional memory functions of the human amygdalaCurrent neurology and neuroscience reports3363364
28 - R Lamprecht, LeDoux J (2004Structural plasticity and memory.Nature reviews54554
29 - M Lehmann, A Douiri, L. G Kim, M Modat, D Chan, S Ourselin, J Barnes, N. C Fox, 2010Atrophy patterns in Alzheimer’s disease and semantic dementia: a comparison of FreeSurfer and manual volumetric measurementsNeuroimage4922642274
30 - Y Liu, T Paajanen, Y Zhang, E Westman, L. O Wahlund, A Simmons, C Tunnard, T Sobow, P Mecocci, M Tsolaki, B Vellas, S Muehlboeck, A Evans, C Spenger, S Lovestone, H Soininen, 2010Analysis of regional MRI volumes and thicknesses as predictors of conversion from mild cognitive impairment to Alzheimer’s disease. Neurobiology of aging 3113751385
31 - C. G Lyketsos, O Lopez, B Jones, A. L Fitzpatrick, J Breitner, S Dekosky, 2002Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.Jama 28814751483
32 - M. S Mega, J. L Cummings, T Fiorello, J Gornbein, 1996The spectrum of behavioral changes in Alzheimer’s disease.Neurology46130135
33 - P Merino-serrais, S Knafo, L Alonso-nanclares, I Fernaud-espinosa, J Defelipe, 2011Layer-specific alterations to CA1 dendritic spines in a mouse model of Alzheimer’s diseaseHippocampus2110371044
34 - M Mesulam, 2004The Cholinergic Lesion of Alzheimer’s Disease: Pivotal Factor or Side Show? Learning & Memory 114349
35 - E Mori, M Ikeda, N Hirono, H Kitagaki, T Imamura, T Shimomura, 1999aAmygdalar volume and emotional memory in Alzheimer’s disease.Am J Psychiatry 156216222
36 - E Mori, M Ikeda, N Hirono, H Kitagaki, T Imamura, T Shimomura, 1999bAmygdalar volume and emotional memory in Alzheimer’s disease.The American journal of psychiatry156216222
37 - K Nashiro, M Mather, 2011Effects of emotional arousal on memory binding in normal aging and Alzheimer’s diseaseThe American journal of psychology124301312
38 - E. K Perry, G Blessed, B. E Tomlinson, R. H Perry, T. J Crow, A. J Cross, G. J Dockray, R Dimaline, A Arregui, 1981Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. Neurobiology of aging 2251256
39 - J. L Price, P. B Davis, J. C Morris, D. L White, 1991The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer’s disease.Neurobiology of aging12295312
40 - G Richter-levin, 2004The amygdala, the hippocampus, and emotional modulation of memory. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 103139
41 - Robins Wahlin TBByrne GJ (2011Personality changes in Alzheimer’s disease: a systematic review.Int J Geriatr Psychiatry 2610191029
42 - C Satler, L. M Garrido, E. P Sarmiento, S Leme, C Conde, C Tomaz, 2007Emotional arousal enhances declarative memory in patients with Alzheimer’s disease.Actaneurologica Scandinavica116355360
43 - G. E Schafe, V Doyere, LeDoux JE (2005Tracking the fear engram: the lateral amygdala is an essential locus of fear memory storage.J Neurosci 251001010014
44 - R. R Schultz, C. C De Castro, P. H Bertolucci, 2009Memory with emotional content, brain amygdala and Alzheimer’s disease. Acta neurologica Scandinavica 120101110
45 - D. J Selkoe, 1996Amyloid beta-protein and the genetics of Alzheimer’s disease. The Journal of biological chemistry 2711829518298
46 - D. J Selkoe, 2002Alzheimer’s disease is a synaptic failure. Science (New YorkNY 298789791
47 - H Shinotoh, K Fukushi, S Nagatsuka, N Tanaka, A Aotsuka, T Ota, H Namba, S Tanada, T Irie, 2003The Amygdala and Alzheimer’s Disease. Annals of the New York Academy of Sciences 985411419
48 - E Solano-castiella, A Schäfer, E Reimer, E Türke, T Pröger, G Lohmann, R Trampel, R Turner, 2011Parcellation of human amygdala in vivo using ultra high field structural MRI. Neuroimage 58741748
49 - T. L Spires, B. T Hyman, 2005Transgenic models of Alzheimer’s disease: Learning from animals.NeuroRx 2423437
50 - T Spires-jones, S Knafo, 2012Spines, Plasticity, and Cognition in Alzheimer’s Model Mice. Neural Plasticity 2012.
51 - M Sundstrom, 2011Modeling recall memory for emotional objects in Alzheimer’s disease.Neuropsychology, development, and cognition Section B, Aging, 2011and cognition 18396413
52 - E Talassi, G Cipriani, A Bianchetti, M Trabucchi, 2007Personality changes in Alzheimer’s disease.Aging Ment Health 11526531
53 - R. D Terry, 2000Cell Death or Synaptic Loss in Alzheimer Disease.Journal of Neuropathology & Experimental Neurology 5911181119
54 - R. D Terry, E Masliah, D. P Salmon, N Butters, R Deteresa, R Hill, L. A Hansen, R Katzman, 1991Physical basis of cognitive alterations in alzheimer’s disease: Synapse loss is the major correlate of cognitive impairment.Annals of neurology30572580
55 - J. W Unger, L. W Lapham, T. H Mcneill, T. A Eskin, R. W Hamill, 1991The amygdala in Alzheimer’s disease: neuropathology and Alz 50 immunoreactivity.Neurobiology of aging12389399
56 - Vasconcelos Lde GJackowski AP, Oliveira MO, Flor YM, Bueno OF, Brucki SM (2011Voxel-based morphometry findings in Alzheimer’s disease: neuropsychiatric symptoms and disability correlations- preliminary results. Clinics (Sao Paulo) 6610451050
57 - Vasconcelos LdGJackowski AP, Oliveira MOd, Flor YMR, Bueno OFA, Brucki SMD (2011Voxel-based morphometry findings in Alzheimer’s disease: neuropsychiatric symptoms and disability correlations- preliminary results. Clinics 6610451050
58 - Vereecken THLGVogels OJM, Nieuwenhuys R Neuron loss and shrinkage in the amygdala in Alzheimer’s disease. Neurobiology of aging 154554
59 - C. I Wright, B. C Dickerson, E Feczko, A Negeira, D Williams, 2007A Functional Magnetic Resonance Imaging Study of Amygdala Responses to Human Faces in Aging and Mild Alzheimer’s DiseaseBiological Psychiatry6213881395