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Cited by 123Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease

Open access
Arnold, Steven E., Louneva, Natalia, Cao, Kajia, Wang, Li-San, Han, Li-Ying, Wolk, David A., Negash, Selamawit, Leurgans, Sue E. +4 more·2013·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2012.03.004PMC PMC3478410
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Abstract

While neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect as some people exhibit normal cognition despite high levels of AD pathology. We compared the cellular, synaptic and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: 1) pathological AD with normal cognition (“AD-Resilient”), 2) pathological AD with AD-typical dementia (“AD-Dementia)” and 3) pathologically normal with normal cognition (“Normal Comparison”). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared to the AD-Dementia group, and increased densities of GFAP astrocytes compared to both the AD-Dementia and Normal Comparison group. Further, in a discovery antibody microarray protein analysis we identified a number of candidate protein abnormalities that were associated with diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD.

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Crossref · 10.1016/j.neurobiolaging.2012.03.004

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 31 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    GFAP astrocyte densities differed among groups, with post-hoc tests showing increased density in the AD-Resilient group compared to both AD-Dementia and Normal Comparison groups.

    “GFAP astrocyte densities differed among groups with post-hoc tests demonstrating increased density in the AD-Resilient group compared to both the AD-Dementia and NC groups.”
    • Also stated in: § Abstract · plain
      “increased densities of GFAP astrocytes compared to both the AD-Dementia and Normal Comparison group.”
    Quote in the paperSubstantial claim
  • Findingown data

    PHFtau neurofibrillary tangles negatively correlated with synaptopodin spines (ρ=−0.45, p=0.01).

    “negatively correlated with synaptopodin spines (ρ=−0.45, p=0.01)”
    Quote in the paperNot a substantial claim
  • Findingown data

    One-way ANOVA identified 57 proteins that distinguished the groups.

    “Using one-way ANOVA, we then identified 57 proteins that distinguished the groups (Table 3), and visualized the proteins in a heat map (Figure 2b).”
    Quote in the paperSubstantial claim
  • Findingown data

    Pre- and postsynaptic measures were highly correlated (Spearman's r = 0.58, p = 0.0009).

    “In accord with their expected relationship, pre- and postsynaptic measures were highly correlated (Spearman’s r = 0.58, p = 0.0009).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Amyloid-β plaques negatively correlated with synaptopodin spines (ρ=−0.44, p=0.02).

    “negatively correlated with synaptopodin spines (ρ=−0.44, p=0.02)”
    Quote in the paperSubstantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 23
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingown data

    Both synaptopodin spines and synaptophysin immunoexpression were preserved in the AD-Resilient group, with levels comparable to the Normal Comparison group.

    “Both synaptopodin spines and synaptophysin immunoexpression were preserved in AD-Resilient group, with levels comparable to those in the NC group.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    PHFtau tangles negatively correlated with NeuN neurons (ρ=−0.31, p=0.10), but this was not statistically significant.

    “Whjle not statistically significant, PHFtau tangles negatively correlated with NeuN neurons (ρ=−0.31, p=0.10)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The Normal Comparison group was especially distinct from AD-Dementia and AD-Resilient groups, but some differentiation in expression pattern between AD-Dementia and AD-Resilient groups was observed.

    “The NC group was especially distinct from AD-Dementia and AD-Resilient groups, but we did observe some differentiation in the expression pattern between AD-Dementia and AD-Resilient groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    PHFtau tangles negatively correlated with synaptophysin (ρ=−0.27, p=0.16), but this was not statistically significant.

    “and synaptophysin (ρ=−0.27, p=0.16).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Brain weights were lower in the AD-Dementia group than in the AD-Resilient and Normal Comparison groups, but the differences were not statistically significant.

    “Brain weights were less in the AD-Dementia group compared to the AD-Resilient and NC groups but differences were not statistically significant (Table 1 and Supplement Figure).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Amyloid-β plaque percent areas and PHFtau neurofibrillary tangle densities in midfrontal cortex were comparable in AD-Resilient and AD-Dementia groups, and both were significantly greater than in the Normal Comparison group.

    “Immunohistochemically labeled amyloid-β plaque % areas and PHFtau neurofibrillary tangle densities in midfrontal cortex were comparable in the AD-Resilient and AD-Dementia groups and both were significantly greater in these groups than the NC group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Significant differences were found among groups in apolipoprotein E ε4 allele frequency, mini-mental state examination score, and CERAD and Braak scores.

    “As expected, significant differences were found in frequency of apolipoprotein E ε4 allele, mini-mental state examination score, and CERAD and Braak scores.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    NeuN neuron density was slightly lower in the Normal Comparison group than in both AD-Resilient and AD-Dementia groups, but the differences were not significant.

    “NeuN neuron density was slightly lower in the NC group compared to both the AD-Resilient and AD-Dementia groups, but differences were not significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Synaptophysin expression was normal in midfrontal cortex in the AD-Resilient group and reduced in the AD-Dementia group.

    “normal synaptophysin expression in midfrontal cortex in the AD-Resilient group indicates preserved connectivity while the reduced synaptophysin expression in the AD-Dementia group suggests decreased connectivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PCA showed tight clustering of component scores for NC cases, whereas AD cases (both AD-Dementia and AD-Resilient) had more variable distributions.

    “It is noteworthy that PCA found tight clustering of component scores of the NC cases while the cases with pathological AD, both AD-Dementia and AD-Resilient, were more variable in their distributions.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Between AD-Resilient and AD-Dementia groups, a difference was observed in serine/threonine-protein phosphatase (PP2A).

    “serine/threonine-protein phosphatase (“PP2A”, an important phosphatase for tau (Iqbal, et al., 2009))”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differentially expressed proteins identified by the antibody microarray are not false positives arising from multiple comparisons.

  • May combine two claims.

    Findingown data

    Density of synaptopodin-labeled spine puncta was lower in AD-Dementia and similar to normal in AD-Resilient.

    “We found synaptopodin-labeled spine puncta density to be reduced in AD-Dementia as well, but densities were equivalent to normal in the AD-Resilient group.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Between AD-Resilient and AD-Dementia groups, a difference was observed in lymphocyte-specific protein tyrosine kinase.

    “lymphocyte-specific protein tyrosine kinase (which phosphorylates tyrosine residues in tau, has been reported to be decreased in AD and genetically associated with AD (Scales, et al., 2011))”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The differentially expressed proteins identified by the antibody microarray are not false positives arising from multiple comparisons.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Amyloid-β plaques and hyperphosphorylated tau tangles are common age-related lesions that are presumed to play primary pathophysiological roles in Alzheimer's disease dementia.

    “Amyloid-β plaques and hyperphosphorylated tau neurofibrillary tangles are common age-related lesions that are presumed to play primary pathophysiological roles in the dementia of Alzheimer’s disease (AD)(Jellinger, 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jellinger, 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Nun Study found that education, diet, linguistic ability, and childhood positive emotion affect late-life cognitive function.

    “For example, the Nun Study has shown discordance of cognition with pathology as well as the important effects of education, diet, linguistic ability, and childhood positive emotion on cognitive function in late life (Iacono, et al., 2009,Tyas, et al., 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Iacono, et al., 2009 source

      Not checked in the free run.

    • cites Tyas, et al., 2007 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Ten cases from each group were filtered to be most closely matched for age and postmortem interval.

    “We then filtered 10 cases from each group that were most closely matched for age and postmortem interval.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Cases with clinical or pathological diagnoses other than normal, mild cognitive impairment, or Alzheimer's disease that could contribute to cognitive impairment were excluded.

    “We excluded any cases with clinical or pathological diagnoses other than normal, MCI or AD that potentially contributed to cognitive impairment (e.g., abundant Lewy body pathology, infarcts, hippocampal sclerosis, etc.).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Independent publications report very high validity of differential protein expression on the Clontech antibody array, verified with Western blotting, and our preliminary findings were consistent with this.

    “Independent publications report very high validity of differential protein expression, verified with Western blotting, and our preliminary study findings were consistent with this.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Anderson, et al., 2003 source

      Not checked in the free run.

    • cites Hatjiharissi, et al., 2007 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Neuropathologic diagnoses of Alzheimer's disease were made by a board-certified neuropathologist blinded to age and all clinical data using NIA-Reagan, Braak, and CERAD classifications.

    “Neuropathologic diagnoses of AD were established by a board-certified neuropathologist blinded to age and all clinical data according to NIA-Reagan (Hyman and Trojanowski, 1997), Braak (Braak and Braak, 1995), and CERAD (Mirra, et al., 1991) classifications.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hyman and Trojanowski, 1997 source

      Not checked in the free run.

    • cites Braak and Braak, 1995

      Not checked in the free run.

    • cites Mirra, et al., 1991 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The midfrontal gyrus cortex was chosen because of its important role in complex cognition and its common neuropathological involvement in Alzheimer's disease.

    “The midfrontal gyrus cortex (corresponding predominantly to Brodmann area 46) was chosen for semi-quantitative image analyses of AD pathology, cellular and synaptic markers because of its important role in complex cognition and its common neuropathological involvement in the spectrum of AD (Arnold, et al., 1991).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Arnold, et al., 1991 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Selected cases were inspected for other clinical data that might skew the pathology-cognition relationship, and alternative cases were substituted as necessary.

    “Finally, we inspected the selected cases for other clinical data that might skew the relationship between pathology and cognition, i.e., unusual medical or psychiatric conditions, medicines, or causes of death, and substituted alternative cases as necessary.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Clinical evaluations in the Religious Orders Study were performed by personnel blinded to previous evaluations.

    “Annual evaluations included a uniform structured interview and examination consisting of medical history, neurological examination and cognitive testing by trained personnel who are blind to previous evaluations, as previously described (Bennett, et al., 2002).”
    • Also stated in: § 2.1 Case Materials · plain
      “Follow-up evaluations, identical in all essential details, were performed annually by examiners blinded to previously collected data.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bennett, et al., 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Image acquisition and analyses were conducted masked to case information.

    “All image acquisition and analyses were conducted masked to case information.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Data were collected in single sections that were all stained in single runs with uniform development times.

    “Data was collected in single sections that were all stained in single runs with uniform development times.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The hemisphere used for diagnostic and frozen blocks alternated randomly between cases.

    “The hemisphere used for diagnostic and frozen blocks alternated randomly between cases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Clontech antibody array has been used in a variety of settings since 2003.

    “The Clontech antibody array has been used in a variety of settings since 2003 (Anderson, et al., 2003,Hatjiharissi, et al., 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Anderson, et al., 2003 source

      Not checked in the free run.

    • cites Hatjiharissi, et al., 2007 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Selection was limited to female participants to minimize sex and major lifestyle differences.

    “We first limited our selection to female participants in the ROS cohort, thus minimizing sex and major lifestyle differences (given relatively similar lifestyles activities, diet, habits and healthcare of Catholic female clergy).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Statistical analyses showed no significant differences among groups for education, hormone replacement therapy use, postmortem interval, brain weight, and presence or absence of macroscopic or microscopic infarcts.

    “Statistical analyses further showed no significant differences among groups for education, use of hormone replacement therapy (only 1 normal comparison case had ever been on this), postmortem interval, brain weight, and presence or absence of macroscopic or microscopic infarcts, which if present, were in regions other than mid-frontal cortex.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The protein expression profile of healthy brain tissue is distinct from that of tissue with abundant Alzheimer's disease pathology, and Alzheimer's disease pathology disrupts protein expression in non-cohesive ways.

    “This suggests that the protein expression profile of healthy brain tissues is distinct from those with abundant AD pathology and that AD pathology disrupts protein expression in non-cohesive ways.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Preliminary microarray experiments showed an average coefficient of variation of 0.14 (SD=0.27, range 0.01 to 2.0) for protein measurements.

    “Preliminary experiments with the microarray were conducted to examine the inter-experiment reliability of the platform. Aliquots of pooled tissue homogenates from two groups were run in four separate experiments and coefficient of variations (CV) were calculated for each of the protein measurements on the array. Average CV was 0.14 (SD=0.27, range 0.01 to 2.0)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Synaptic loss is often considered the strongest neuropathological correlate of dementia severity in Alzheimer's disease and is linked to amyloid-β and tau pathology.

    “Synaptic loss is frequently cited as the best neuropathological correlate of dementia severity in AD (Terry, et al., 1991) and has been linked to the accumulation of both amyloid-β and tau pathology (Arendt, 2009).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Terry, et al., 1991 source

      Not checked in the free run.

    • cites Arendt, 2009 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Cortical astrocytes support brain health through structural, biochemical, and regulatory functions, including ion balance, nutrient supply, blood flow regulation, transmitter uptake and release, synaptic modulation, and trophic and detoxifying support.

    “Cortical astrocytes maintain brain health through structural and biochemical support to neurons and endothelial cells, maintain extracellular ion balance, provide nutrients to neurons, regulate cortical blood flow, transmitter uptake and release, modulate synaptic neurotransmission and provide trophic and detoxifying support in response to injury (Sofroniew and Vinters, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sofroniew and Vinters, 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological Alzheimer's disease.

    “These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 507 proteins measured by the Clontech antibody microarray include proteins relevant to resilient cognition in Alzheimer’s disease.

  • May combine two claims.

    Premisecitation

    In preclinical Alzheimer's disease cases, there is no measurable cognitive impairment per se, but cognitive function is degraded in the presence of plaques and tangles.

    “Supporting this notion, Price et al. reported no measureable cognitive impairment per se in such preclinical AD cases, but degraded cognitive function in the presence of plaques and tangles (Price, et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Price, et al., 2009 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    An antibody microarray provided an unbiased measurement of relative expression for more than 500 proteins across diverse functional groups.

    “An antibody microarray served as an unbiased measure of the relative expression levels of over 500 proteins that span a broad range of functional groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    These methods could introduce systematic inaccuracies that reference volume-based stereology might avoid.

    “However, they may introduce systematic inaccuracies that might be obviated with reference volume-based stereological approaches.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Multiple comparisons remain a challenge, particularly with small sample sizes.

    “but the challenge of multiple comparisons remains, especially in relatively small sample sizes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Postmortem neuropathology provides only a near-death snapshot, can suggest but not establish causal links between clinical and brain data, and confounds like agonal state and postmortem changes can alter cellular and molecular integrity.

    “while postmortem neuropathology remains the best approach to investigate the neurobiology of uniquely human brain diseases, it only allows a snapshot of the brain as it was near the time of death, it can suggest, but not establish, causal relationships between clinical and brain data, and confounds such as agonal state and postmortem changes can alter the brains’ cellular and molecular integrity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Using a pooled tissue standard, dye swapping, and calculated INR reduced many potential pitfalls.

    “Our use of a pooled tissue standard as a reference in all experiments, dye swapping and calculated INR attenuated many potential pitfalls”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Automated computer-assisted analyses reduce operator bias, are suitable for larger high-throughput studies, and successfully detected between-group differences.

    “These minimize operator bias, lend themselves well to larger scale, high-throughput studies, and they successfully found between group differences.”
    Quote in the paperNot a substantial claim
40 of 40

  • The paper relies on this without support.

    There has been little postmortem investigation of neurobiological factors that might confer or be associated with resilient brain aging.

    “Aside from noting such discordance in clinicopathological studies, there has been little pursuant postmortem investigation of neurobiological factors that might confer or be associated with resilient brain aging.”

  • The paper relies on this without support.

    The correlation between Alzheimer’s disease neuropathological lesions and cognition is modest and accounts for limited variance among older adults.

    “However, it is also recognized that the correlation between these neuropathological lesions and cognition is modest and accounts for a limited amount of the variance of cognition among older adults.”

  • The paper relies on this without support.

    The 507 proteins measured by the Clontech antibody microarray include proteins relevant to resilient cognition in Alzheimer’s disease.

    “The Clontech. Antibody Microarray 500 (Clontech, Mountainview, CA) was used to profile relative expression levels of 507 proteins.”

  • The paper relies on this without support.

    Composite cognition scores from the last assessment before death accurately reflect the participants’ cognitive status relevant to group classification.

    “We next stratified according to composite cognition scores from the last assessment before death and global pathology (average plaque and tangle burdens in diagnostic blocks).”

  • The paper relies on this without support.

    The observed cellular and biochemical differences between the AD-Resilient group and the other groups are not attributable to confounds such as agonal state or postmortem changes.

    “confounds such as agonal state and postmortem changes can alter the brains’ cellular and molecular integrity.”

  • The paper relies on this without support.

    The differentially expressed proteins identified by the antibody microarray are not false positives arising from multiple comparisons.

    “the challenge of multiple comparisons remains, especially in relatively small sample sizes.”
6 of 6

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Authors
Arnold, S. E., Louneva, N., Cao, K., Wang, L.-S., Han, L.-Y., Wolk, D. A., Negash, S., Leurgans, S. E., Schneider, J. A., Buchman, A. S., Wilson, R. S., & Bennett, D. A.
Affiliations
  • University of Pennsylvania (US)
  • Rush University (US)
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2013-01
Volume
34
Issue
1
Pages
157-168
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2012.03.004
PMC
PMC3478410
OpenAlex
W2046582067
Semantic Scholar
35b7b967d421550d0fbfcd374180037594e42757
Cited by
123
References
66
Citations by year
2026: 7 · 2025: 18 · 2024: 5 · 2023: 10 · 2022: 17 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 3 · 2014: 9 · 2013: 9 · 2012: 1
FWCI
4.72
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG039478, R01AG15819, P30AG10161, P30AG10124)
  • Marian S. Ware Alzheimer's Program/National Philanthropic Trust
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, cognitive resilience, synaptophysin, synaptopodin, presynaptic terminals, dendritic spines, astrocytes, glial fibrillary acidic protein, antibody microarrays, protein biomarkers, dementia, Religious Orders Study, brain aging
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Female, Glial Fibrillary Acidic Protein, Humans, Male, Nerve Tissue Proteins, Neurons, Phosphopyruvate Hydratase, Synapses, tau Proteins, Protein Array Analysis, Microscopy, Electron, Transmission

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