Journal Article

DZNE-2026-00968

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Health-related factors and their impact on blood-based biomarkers of Alzheimer's disease

Kurz, C. ; Taute, M. ; Tegethoff, P. ; Hufnagel, A.Extern* ; Leonhardt, S. ; Gürsel, S. Ü.DZNE* ; Koriath, C. ; Jethwa, A. ; Kollmorgen, G. ; Bittner, T. ; Keeser, D. ; Brendel, M.Extern* ; Haeckert, J. ; Utecht, J. ; Papazov, B. ; Levin, J.DZNE* ; Höglinger, G.DZNE* ; Rauchmann, B.-S.DZNE* ; Perneczky, R. (Last author)DZNE*

2026
Elsevier Amsterdam

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Please use a persistent id in citations: doi:10.1016/j.nbas.2026.100166

Abstract: Background: Health-related factors may influence blood-based biomarkers (BBBM) of Alzheimer's disease (AD). In this analysis, associations between modifiable factors and plasma biomarkers of neurodegeneration were investigated across the Alzheimer's disease spectrum and in cognitively healthy controls in a cerebrospinal fluid–confirmed (CSF) cohort. Methods: Plasma biomarkers included the Aβ1–42/1–40 ratio, pTau181, GFAP, NFL and ApoE4. Multiple linear regression was used to test associations with lifestyle factors (physical activity and sleep), physiological factors (including renal and lipid metabolism markers), genetic factors (APOE ε4), age and sex. Percentage effect sizes and confidence intervals were calculated. Results: The study included CSF-characterized individuals with AD (mild cognitive impairment due to AD and AD dementia) and cognitively healthy controls (n = 116; mean age 71.2 years). Overall, the associations were modest, with wide confidence intervals reflecting variability in the outcomes and the limited range of predictors in this relatively healthy sample. In CSF-confirmed participants, age emerged as the most consistent predictor of plasma biomarker levels, particularly NFL and pTau181. APOE ε3/ε4 genotype was additionally associated with higher pTau181 levels. Other demographic, metabolic and lifestyle-related variables showed only weak or inconsistent associations. Conclusion: To implement BBBM in broader populations, a systematic evaluation of confounders is required. As aging cohorts present with mixed pathologies, strategies to address heterogeneity will be essential. The limited number of robust associations observed suggests that plasma biomarkers are influenced primarily by age and genetic background rather than by metabolic factors in this cohort. Validation in more diverse populations remains warranted.

Keyword(s): Alzheimer's disease/blood ; Apolipoproteins E/blood ; Biomarkers/blood ; Neurofilament proteins/blood ; Tau proteins/blood

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
2. Clinical Research (Munich) (Clinical Research (Munich))
3. Clinical Neurodegeneration (AG Levin)
4. Molecular Neurobiology (AG Simons)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2026

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Emerging Sources Citation Index ; Fees ; PubMed Central ; SCOPUS ; Web of Science Core Collection

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