Blood-based protein mediators of senility with replications across biofluids and cohorts.

aging cognition dementia g intelligence

Journal

Brain communications

ISSN: 2632-1297

Titre abrégé: Brain Commun

Pays: England

ID NLM: 101755125

Informations de publication

Date de publication:
2020

Historique:

received: 05 08 2019

revised: 25 09 2019

accepted: 07 10 2019

entrez: 21 9 2020

pubmed: 22 9 2020

medline: 22 9 2020

Statut: epublish

Résumé

Dementia severity can be quantitatively described by the latent dementia phenotype 'δ' and its various composite 'homologues'. We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium. However, it would be convenient to replicate them in the Alzheimer's Disease Neuroimaging Initiative. To that end, we have engineered a δ homologue from the observed cognitive performance measures common to both projects [i.e. 'd:Texas Alzheimer's Research and Care Consortium to Alzheimer's Disease Neuroimaging Initiative' (dT2A)]. In this analysis, we confirm 13/22 serum proteins as partial mediators of age's effect on dementia severity as measured by dT2A in the Texas Alzheimer's Research and Care Consortium and then replicate 4/13 in the Alzheimer's Disease Neuroimaging Initiative's plasma data. The replicated mediators of age-specific effects on dementia severity are adiponectin, follicle-stimulating hormone, pancreatic polypeptide and resistin. In their aggregate, the 13 confirmed age-specific mediators suggest that 'cognitive frailty' pays a role in dementia severity as measured by δ. We provide both discriminant and concordant support for that hypothesis. Weight, calculated low-density lipoprotein and body mass index are partial mediators of age's effect in the Texas Alzheimer's Research and Care Consortium. Biomarkers related to other disease processes (e.g. cerebrospinal fluid Alzheimer's disease-specific biomarkers in the Alzheimer's Disease Neuroimaging Initiative) are not. It now appears that dementia severity is the sum of multiple independent processes impacting δ. Each may have a unique set of mediating biomarkers. Age's unique effect appears to be at least partially mediated through proteins related to frailty. Age-specific mediation effects can be replicated across cohorts and biofluids. These proteins may offer targets for the remediation of age-specific cognitive decline (aka 'senility'), help distinguish it from other determinants of dementia severity and/or provide clues to the biology of Aging Proper.

Identifiants

DOI: 10.1093/braincomms/fcz036 PMID: 32954311 PMC: PMC7425523

pubmed: 32954311

doi: 10.1093/braincomms/fcz036

pii: fcz036

pmc: PMC7425523

doi:

Types de publication

Journal Article

Langues

eng

Pagination

fcz036

Subventions

Organisme : NIA NIH HHS

ID : U01 AG024904

Pays : United States

Informations de copyright

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