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Cited by 198Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Dendritic spines provide cognitive resilience against A lzheimer's disease

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Boros, Benjamin D., Greathouse, Kelsey M., Gentry, Erik G., Curtis, Kendall A., Birchall, Elizabeth L., Gearing, Marla, Herskowitz, Jeremy H.·2017·Annals of Neurology
DOI 10.1002/ana.25049PMC PMC5744899
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Abstract

Objective: Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology, structural changes in dendritic spines would distinguish individuals who had or did not have clinical dementia. Methods: We compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 dorsolateral prefrontal cortex using the Golgi–Cox technique in 12 age‐matched pathology‐free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from bright‐field microscopy images that enabled accurate 3‐dimensional digital reconstruction of dendritic structure for morphologic analyses. Results: Spine density was similar among control and CAD cases but was reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging. Interpretation: These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. Ann Neurol 2017;82:602–614

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  • Dendritic spine density in the dorsolateral prefrontal cortex is inversely correlated with Braak stage in Alzheimer's disease, suggesting that tau pathology may be associated with spine loss.

    “Notably, dendritic spine density in the dorsolateral prefrontal cortex is inversely correlated with Braak stage in AD, suggesting that tau pathology may be associated with spine loss (Boros et al., 2017, Boros et al., 2019).”

    From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Boros et al., 2017

    The Results report an inverse correlation between dorsolateral prefrontal cortex spine density and Braak stage across all cases, but explicitly state that there was no such correlation among AD cases. The Discussion reiterates that distinction. Thus, the paper does not support the claim that the inverse correlation was found in AD cases. (LLM, conf=0.90)

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  • In AD cases, dendritic and synaptic structural remodeling could represent compensatory plasticity responses during the transition from no cognitive impairment to MCI.

    “Notably, in AD cases, dendritic and synaptic structural remodeling could represent compensatory plasticity responses during the transition from no cognitive impairment to MCI (Boros et al., 2017, Boros et al., 2019), and our data suggest these architectural changes could be driven by tau-related disease processes.”

    From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Boros et al., 2017

    The Discussion says the observed spine changes could reflect synaptic structural changes during a transition from preclinical to symptomatic AD, which supports the proposed compensatory-plasticity interpretation. But the study compared cognitively normal people with AD pathology against people with AD dementia; it did not examine a transition specifically to MCI. The Discussion mentions MCI only as a possible outcome in an imaging study. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Synapse or dendritic spine loss correlates more strongly with cognitive impairment than amyloid-β plaques or neurofibrillary tangles in Alzheimer's disease.

    “Synapse or dendritic spine loss correlates more strongly with cognitive impairment than Aβ plaques or NFTs in AD (DeKosky and Scheff, 1990, Terry et al., 1991, Boros et al., 2017, Chen et al., 2018).”

    From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Boros et al., 2017

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Research works printed but not linked: 29

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Authors
Boros, B. D., Greathouse, K. M., Gentry, E. G., Curtis, K. A., Birchall, E. L., Gearing, M., & Herskowitz, J. H.
Affiliations
  • University of Alabama at Birmingham (US)
  • Emory University (US)
Corresponding author
Herskowitz, Jeremy H.
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2017-10
Volume
82
Issue
4
Pages
602-614
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.25049
PMC
PMC5744899
OpenAlex
W2755806383
Cited by
198
References
10
Citations by year
2026: 17 · 2025: 25 · 2024: 24 · 2023: 29 · 2022: 23 · 2021: 20 · 2020: 28 · 2019: 19 · 2018: 13
FWCI
11.67
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 21 d)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (AG054719, AG043552‐05)
  • Alzheimer's Association
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
dendritic spines, Alzheimer's disease, cognitive resilience, prefrontal cortex, dorsolateral prefrontal cortex, pyramidal neurons, dendritic spine morphology, neuritic plaques, Braak staging, dendritic plasticity, preclinical Alzheimer's disease
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Cognition, Female, Hippocampus, Humans, Male, Mental Status Schedule, Middle Aged, Neurons, Linear Models, Case-Control Studies, Silver Staining, Imaging, Three-Dimensional, Dendritic Spines, Neuroimaging

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