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Proteome-wide Analyses Identified Cortical Proteins Associated With Resilience for Varied Cognitive Abilities.
Zammit, Andrea R; Klein, Hans-Ulrich; Yu, Lei; Levey, Allan I; Seyfried, Nicholas T; Wingo, Aliza P; Wingo, Thomas S; Schneider, Julie A; Bennett, David A; Buchman, Aron S.
Affiliation
  • Zammit AR; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Klein HU; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Yu L; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Levey AI; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Seyfried NT; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Wingo AP; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Wingo TS; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Schneider JA; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Bennett DA; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
  • Buchman AS; From the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.
Neurology ; 102(1): e207816, 2024 Jan 09.
Article in En | MEDLINE | ID: mdl-38165375
ABSTRACT
BACKGROUND AND

OBJECTIVES:

Prior work suggests that cognitive resilience may contribute to the heterogeneity of cognitive decline. This study examined whether distinct cortical proteins provide resilience for different cognitive abilities.

METHODS:

Participants were from the Religious Orders Study or the Rush Memory and Aging Project who had undergone annual assessments of 5 cognitive abilities and postmortem assessment of 9 Alzheimer disease and related dementia (ADRD) pathologies. Proteome-wide examination of the dorsolateral prefrontal cortex using tandem mass tag and liquid chromatography-mass spectrometry yielded 8,425 high-abundance proteins. We applied linear mixed-effect models to quantify residual cognitive change (cognitive resilience) of 5 cognitive abilities by regressing out cognitive decline related to age, sex, education, and indices of ADRD pathologies. Then we added terms for each of the individual proteins to identify cognitive resilience proteins associated with the different cognitive abilities.

RESULTS:

We included 604 decedents (69% female; mean age at death = 89 years) with proteomic data. A total of 47 cortical proteins that provide cognitive resilience were identified 22 were associated with specific cognitive abilities, and 25 were common to at least 2 cognitive abilities. NRN1 was the only protein that was associated with more than 2 cognitive abilities (semantic memory estimate = 0.020, SE = 0.004, p = 2.2 × 10-6; episodic memory estimate = 0.029, SE = 0.004, p = 5.8 × 10-1; and working memory estimate = 0.021, SE = 0.004, p = 1.2 × 10-7). Exploratory gene ontology analysis suggested that among top molecular pathways, mitochondrial translation was a molecular mechanism providing resilience in episodic memory, while nuclear-transcribed messenger RNA catabolic processes provided resilience in working memory.

DISCUSSION:

This study identified cortical proteins associated with various cognitive abilities. Differential associations across abilities may reflect distinct underlying biological pathways. These data provide potential high-value targets for further mechanistic and drug discovery studies to develop targeted treatments to prevent loss of cognition.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neuropeptides / Resilience, Psychological / Memory, Episodic Type of study: Risk_factors_studies Limits: Aged80 / Female / Humans / Male Language: En Journal: Neurology Year: 2024 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neuropeptides / Resilience, Psychological / Memory, Episodic Type of study: Risk_factors_studies Limits: Aged80 / Female / Humans / Male Language: En Journal: Neurology Year: 2024 Document type: Article