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Cited by 68Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Translational approaches to understanding resilience to Alzheimer’s disease

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Neuner, Sarah M., Telpoukhovskaia, Maria, Menon, Vilas, O’Connell, Kristen M.S., Hohman, Timothy J., Kaczorowski, Catherine C.·2022·Trends in Neurosciences
DOI 10.1016/j.tins.2022.02.005PMC PMC9035083
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Abstract

Individuals who maintain cognitive function despite high levels of Alzheimer's disease (AD)-associated pathology are said to be 'resilient' to AD. Identifying mechanisms underlying resilience represents an exciting therapeutic opportunity. Human studies have identified a number of molecular and genetic factors associated with resilience, but the complexity of these cohorts prohibits a complete understanding of which factors are causal or simply correlated with resilience. Genetically and phenotypically diverse mouse models of AD provide new and translationally relevant opportunities to identify and prioritize new resilience mechanisms for further cross-species investigation. This review will discuss insights into resilience gained from both human and animal studies and highlight future approaches that may help translate these insights into therapeutics designed to prevent or delay AD-related dementia.

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  • The absence of dementia in AsymAD individuals is partly due to synaptic preservation and, hence, neuron survival.

    “It is well established that the absence of dementia in AsymAD individuals is partly due to synaptic preservation and, hence, neuron survival [31, 67].”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [67]

    The “Features of resilient individuals” section reports preserved synaptic markers and neuron numbers in pathology-positive people without dementia, and the “Concluding remarks” identify maintained synapse structure as a contributor to resilience. The paper does not establish the claimed causal step that synaptic preservation leads to neuron survival; it reports the two forms of preservation together. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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References 95 · Cited by 68

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Authors
Neuner, S. M., Telpoukhovskaia, M., Menon, V., O’Connell, K. M. S., Hohman, T. J., & Kaczorowski, C. C.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Jackson Laboratory (US)
  • Columbia University Irving Medical Center (US)
  • Tufts University (US)
  • Vanderbilt University Medical Center (US)
Corresponding author
Kaczorowski, Catherine C.
ORCID
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2022-05
Volume
45
Issue
5
Pages
369-383
ISSN
0166-2236 (ISSN-L)
DOI
10.1016/j.tins.2022.02.005
PMC
PMC9035083
OpenAlex
W4220663587
Cited by
68
References
95
Citations by year
2026: 9 · 2025: 20 · 2024: 17 · 2023: 19 · 2022: 3
FWCI
2.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Trends in Neurosciences (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion, cc-by)
Funders
National Institute on Aging (R01AG057914, R01AG059716, RF1AG059778, R01AG061518, RF1AG063755, F32AG069503, R01AG054180, R01AG066831, R01AG074012)
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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, cognitive resilience, mouse models of Alzheimer's disease, genetic risk factors, dementia prevention, translational research, cross-species translation, therapeutic target
MeSH terms
Alzheimer Disease, Animals, Brain, Cognition, Humans, Protein Processing, Post-Translational, Mice, Resilience, Psychological

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