Blood Biomarkers of Alzheimer’s Disease Predict Long-Term Muscle Strength Decline in Older Adults

Highlight

• Blood biomarkers linked to Alzheimer’s disease (p-tau181, p-tau217, neurofilament light chain, GFAP) correlate with accelerated decline in muscle strength over 12 years in older adults.
• Associations between biomarkers and muscle decline are partially influenced by cognitive function, suggesting overlapping neurodegenerative and muscular aging pathways.
• Women demonstrate stronger associations than men, particularly in chair-stand performance decline linked to Alzheimer’s biomarkers.
• These biomarkers may serve as early indicators to identify individuals at risk for sarcopenia and target interventions effectively.

Background

Age-related muscle strength decline, or sarcopenia, impairs functional independence and quality of life in older adults. Identifying biological markers that predict muscle deterioration is critical for enabling early prevention and intervention strategies. Alzheimer’s disease (AD) pathology, historically studied in the context of cognitive decline, has increasingly been implicated in physical function deterioration as well. The relationship between blood-based AD biomarkers and longitudinal muscle strength has not been thoroughly explored. This study addresses this gap by investigating how Alzheimer’s disease-related blood biomarkers relate to 12-year trajectories of muscle strength decline in a large cohort of community-dwelling older adults and exploring the modifying influence of cognition on this association.

Study Design

The current investigation is based on the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), a large ongoing prospective cohort study comprising adults aged 60 years and older from central Stockholm, Sweden. Data from the baseline visit (from March 21, 2001) through the fourth follow-up (up to December 31, 2016) were included.

A total of 1953 dementia-free, community-dwelling participants (mean age 70.2 years, 60.1% female) with available blood samples were included. Seven blood biomarkers related to Alzheimer’s pathology were measured at baseline: total tau, phosphorylated tau at threonine 181 (p-tau181), phosphorylated tau at threonine 217 (p-tau217), amyloid beta 40 (Aβ40), amyloid beta 42 (Aβ42), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).

Muscle strength outcomes included handgrip strength and the chair-stand test, measured longitudinally over 12 years. Statistical analyses utilized linear mixed-effects models to assess associations between baseline biomarker concentrations and muscle strength trajectories, adjusting for potential confounders including age, sex, education, and the Mini-Mental State Examination (MMSE) scores to account for cognitive status.

Key Findings

Higher baseline concentrations of specific Alzheimer’s disease biomarkers—namely p-tau181, p-tau217, NfL, and GFAP—were significantly associated with an accelerated decline of muscle strength as measured by the chair-stand test over 12 years. The effect sizes were notable, with p-tau217 showing the strongest association (β per year 1.31, 95% CI 1.03 to 1.58; p<0.0001). Adjusting for MMSE scores diminished but did not completely eliminate these associations, indicating that cognitive decline partly mediates the relationship between AD pathology and muscle strength deterioration.

For handgrip strength, higher levels of p-tau181, p-tau217, and NfL correlated with faster strength decline. Interestingly, adjusting for cognitive function via MMSE did not attenuate these associations, suggesting a degree of independence from overt cognitive impairment.

Sex differences were evident. Female participants exhibited stronger links between higher biomarker concentrations and decline in chair-stand performance compared with males, suggesting possible sex-specific vulnerability or differences in neuro-muscular aging pathways.

Amyloid beta 40 and 42 and total tau did not show consistent associations with muscle strength decline, refining the understanding of which AD-related biomarkers may be most relevant for muscular aging.

Expert Commentary

These findings shed light on the biological intersection between neurodegenerative processes and physical frailty in aging. The observation that phosphorylated tau species and neurofilament light chain—markers reflecting neurofibrillary tangle pathology and neuroaxonal damage—predict muscle decline underscores the systemic impact of AD pathology beyond the brain. The partial mediation by cognitive status highlights the intertwined trajectories of brain and muscle aging.

Sex differences raise intriguing questions about hormonal, genetic, or lifestyle factors that might modulate vulnerability to neuromuscular decline in relation to AD pathology. Clinicians should consider these biomarkers as part of an emerging toolkit to stratify risk for sarcopenia, potentially guiding earlier and personalized preventive interventions.

Limitations include the observational design, which cannot establish causality, and the generalizability limited to a relatively homogeneous Swedish population. Future studies should explore mechanistic pathways and intervention trials targeting these biomarker-positive individuals.

Conclusions

Blood biomarkers associated with Alzheimer’s disease pathology, particularly phosphorylated tau species and neurofilament light chain, are promising predictors of accelerated muscle strength decline over 12 years in older adults. The interaction with cognitive function suggests a shared or overlapping neurodegenerative and muscle aging process. These biomarkers could be incorporated into clinical assessments to identify older adults at risk for sarcopenia and implement early, targeted interventions to promote healthy aging and preserve functional independence.

Funding

This work was supported by the Swedish Research Council, the Swedish Ministry of Health and Social Affairs, and County Councils and Municipalities.

References

Ornago AM, Pinardi E, Grande G, et al. Blood biomarkers of Alzheimer’s disease and 12-year muscle strength trajectories in community-dwelling older adults: a cohort study. Lancet Healthy Longev. 2025;6(5):100715. doi:10.1016/j.lanhl.2025.100715. Epub 2025 May 22. PMID: 40414227.