Blood-based Alzheimer's disease biomarkers and cognitive decline in essential tremor

Document Type

Article

Publication Date

2-1-2026

Publication Title

Journal of Alzheimer's disease

Keywords

Humans, Essential Tremor, Male, Biomarkers, Female, Aged, 80 and over, Cognitive Dysfunction, Alzheimer Disease, tau Proteins, Aged, Glial Fibrillary Acidic Protein, Amyloid beta-Peptides, Neurofilament Proteins, Neuropsychological Tests, Peptide Fragments

Abstract

Background: Two epidemiological studies demonstrated an association between essential tremor (ET) and prevalent dementia as well as substantially elevated risks of incident dementia among ET cases. At this early point, the underlying pathophysiology of ET-dementia is not known. In vivo biomarkers of Alzheimer's disease (AD) and neurodegeneration could help bridge the gap between the pathophysiological processes that present in the context of ET-dementia.

Objective: Examine blood concentrations of t-tau, p-tau181, p-tau217, Aβ(42/40), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ET with a range of cognitive diagnoses.Methods40 ET cases (mean age = 81.5 ± 7.3; including 20 normal cognition (NC), 12 cognitively normal with some weaknesses, 4 mild cognitive impairment, and 4 dementia) were enrolled in a study of cognitive performance in ET, during which phlebotomy was performed.

Results: Greater cognitive difficulty was associated with higher blood concentrations of p-tau217, p-tau181, GFAP, and NfL, and a lower Aβ(42/40) ratio (p tests for trend <  0.05). Cases with dementia had marginally higher concentrations of p-tau217 (p = 0.06) and higher concentrations of GFAP and NfL (p <  0.05) than cases with NC. Furthermore, higher concentrations of p-tau217, GFAP, and NfL were associated with lower cognitive test scores across multiple cognitive domains (p <  0.05).

Conclusions: Albeit based on a small sample of cases, our findings suggest a potential role of blood-based biomarkers as markers for cognitive function in ET patients. Cognitive decline in ET may be due to underlying neurodegenerative processes involving tau and perhaps Aβ pathology.

Medical Subject Headings

Humans; Essential Tremor; Male; Biomarkers; Female; Aged, 80 and over; Cognitive Dysfunction; Alzheimer Disease; tau Proteins; Aged; Glial Fibrillary Acidic Protein; Amyloid beta-Peptides; Neurofilament Proteins; Neuropsychological Tests; Peptide Fragments

PubMed ID

41384822

ePublication

ePub ahead of print

Volume

109

Issue

3

First Page

1232

Last Page

1241

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