Year: 2023
Type: article
Abstract: BACKGROUND: Alzheimer's disease and related dementias (ADRD) involve biological processes that begin years to decades before onset of clinical symptoms. The plasma proteome can offer insight into brain aging and risk of incident dementia among cognitively healthy adults. OBJECTIVE: To identify biomarkers and biological pathways associated with neuroimaging measures and incident dementia in two large community-based cohorts by applying a correlation-based network analysis to the plasma proteome. METHODS: Weighted co-expression network analysis of 1,305 plasma proteins identified four modules of co-expressed proteins, which were related to MRI brain volumes and risk of incident dementia over a median 20-year follow-up in Framingham Heart Study (FHS) Offspring cohort participants (n = 1,861). Analyses were replicated in the Cardiovascular Health Study (CHS) (n = 2,117, mean 6-year follow-up). RESULTS: Two proteomic modules, one related to protein clearance and synaptic maintenance (M2) and a second to inflammation (M4), were associated with total brain volume in FHS (M2: p = 0.014; M4: p = 4.2×10-5). These modules were not significantly associated with hippocampal volume, white matter hyperintensities, or incident all-cause or AD dementia. Associations with TCBV did not replicate in CHS, an older cohort with a greater burden of comorbidities. CONCLUSIONS: Proteome networks implicate an early role for biological pathways involving inflammation and synaptic function in preclinical brain atrophy, with implications for clinical dementia.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-230145
Authors: Meghan I. Short, Alison E. Fohner, Håvard K. Skjellegrind, Alexa Beiser, Mitzi M. Gonzales, Claudia L. Satizabal, Thomas R. Austin, W.T. Longstreth, Joshua C. Bis, Oscar Lopez, Kristian Hveem, Geir Selbæk, Martin G. Larson, Qiong Yang, Hugo J. Aparicio, Emer R. McGrath, Robert E. Gerszten, Charles S. DeCarli, Bruce M. Psaty, Ramachandran S. Vasan, Habil Zare, Sudha Seshadri
Institutions: Tufts University, Tufts Medical Center, The University of Texas at San Antonio Health Science Center, University of Washington, Norwegian University of Science and Technology, Levanger Hospital, Helse Nord-Trøndelag HF, Boston University, Framingham Heart Study, University of Pittsburgh, Oslo University Hospital, Sykehuset i Vestfold, Norwegian National Centre for Ageing and Health, Ollscoil na Gaillimhe – University of Galway, Broad Institute, Beth Israel Deaconess Medical Center, Harvard University, Massachusetts Institute of Technology, University of California, Davis
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Alzheimer's Association, School of Medicine, Boston University, Health Research Board, Evans Medical Foundation, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: G1002540797, G101103092, G1023702118, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, UC Davis Alzheimer's Disease Core Center, G1353455142, CORONARY HEART DISEASE AND STROKE, G1642866419, G247538147, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G2662099513, G2675915175, G343469054, G34347772, CHS research resources for the cardiovascular health of older adults, Proteomic Pathway Discovery in Cardiovascular Disease, G36433118, Plasma proteomics in CHS and population biology, Predictors of Alheimers Disease in Mild Cognitive Impairment, G423252844, G5370164845, G581887176, CHS Events Follow-up Study, CHS-Transition Phase, G683723002, G7441165371, Blood Biomarkers for Prediction of Vascular Cognitive Impairment & Dementia, Integrated multi-omics approach to identify early protein biomarkers in Alzheimer's disease and cognitive decline, Tufts Clinical and Translational Science Institute, G905887895
OpenAlex ID: W4388967486