Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets

Author:

Varma Curran1ORCID,Luo Eva1,Bostrom Gustaf1234,Bathini Praveen12,Berdnik Daniela5,Wyss‐Coray Tony5,Zhao Tingting6,Dong Xianjun127,Ervin Frank R.89,Beierschmitt Amy810,Palmour Roberta M.89,Lemere Cynthia A.12

Affiliation:

1. Department of Neurology Ann Romney Center for Neurologic Diseases Brigham and Women's Hospital Boston Massachusetts USA

2. Department of Neurology Harvard Medical School Boston Massachusetts USA

3. Department of Public Health and Caring Sciences Geriatrics, Uppsala University Uppsala Sweden

4. Centre for Clinical Research Uppsala University Västmanland County Hospital Västerås Sweden

5. Department of Neurology and Neurological Sciences Stanford University School of Medicine Stanford California USA

6. Department of Medical Oncology Dana‐Farber Cancer Institute Boston Massachusetts USA

7. Genomics and Bioinformatics Hub Brigham and Women's Hospital Boston Massachusetts USA

8. Behavioral Sciences Foundation Saint Kitts, Eastern Caribbean Montreal Canada

9. Faculty of Medicine and Health Sciences McGill University Montreal Canada

10. Department of Biomedical Sciences Ross University School of Veterinary Medicine St Kitts UK

Abstract

AbstractINTRODUCTIONVervets are non‐human primates that share high genetic homology with humans and develop amyloid beta (Aβ) pathology with aging. We expand current knowledge by examining Aβ pathology, aging, cognition, and biomarker proteomics.METHODSAmyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old age was quantified. We also obtained cognitive scores, plasma samples, and cerebrospinal fluid (CSF) samples in additional animals. Plasma and CSF proteins were quantified with platforms utilizing human antibodies.RESULTSWe found age‐related increases in Aβ deposition in both brain regions. Bioinformatic analyses assessed associations between biomarkers and age, sex, cognition, and CSF Aβ levels, revealing changes in proteins related to immune‐related inflammation, metabolism, and cellular processes.DISCUSSIONVervets are an effective model of aging and early‐stage Alzheimer's disease, and we provide translational biomarker data that both align with previous results in humans and provide a basis for future investigations.Highlights We found changes in immune and metabolic plasma biomarkers associated with age and cognition. Cerebrospinal fluid (CSF) biomarkers revealed changes in cell signaling indicative of adaptative processes. TNFRSF19 (TROY) and Artemin co‐localize with Alzheimer's disease pathology. Vervets are a relevant model for translational studies of early‐stage Alzheimer's disease.

Funder

National Aeronautics and Space Administration

Publisher

Wiley

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