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Does subclinical peripheral health influence Alzheimer’s disease?
November 23, 2023
Does subclinical peripheral health influence Alzheimer’s disease?
Protein indicators of subclinical health are linked to markers of Alzheimer’s disease (AD) and neurodegeneration, according to research published in the journal Annals of Neurology. The authors found that protein-based indicators of risk for cardiovascular disease, heart failure mortality, and kidney disease were associated with plasma biomarkers linked to AD, including amyloid-beta, phosphorylated tau181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP), even in individuals not diagnosed with cardiovascular or kidney disease. (Dark, 2023)
The link between health risk and Alzheimer’s disease biomarkers
Prior studies have suggested that peripheral disease, including hypertension and obesity, is associated with cognitive decline and the risk of AD. However, less is known about how peripheral health factors influence the pathology and nonspecific features of AD, such as neuronal damage and astrogliosis.
To investigate this, Keenan Walker, PhD, of the National Institute on Aging in Baltimore and his coauthors aimed to assess the possible effects of health traits, disease, and disease risk on blood-based biomarkers of AD and neurodegeneration.
Walker and his colleagues examined 14 protein-based health indicators of AD pathology, including amyloid-beta, phosphorylated tau181 (p-tau181), neurofilament light (NfL, a marker of neuronal injury), and glial fibrillary acidic protein (GFAP), a measure of astrogliosis. Plasma and neuroimaging measurements of AD and neurodegeneration were also included.
These plasma biomarkers of neurodegeneration are widely used and provide a broad, dynamic picture of health across multiple organ systems in a scalable manner. By analyzing these proteomic signatures of health and disease, clinicians could potentially detect and quantify subthreshold disease and disease risk in individuals without clinically defined disease. The data could also assist researchers in identifying effective prevention and therapeutic interventions.
The study’s main cohort was assembled from the Baltimore Longitudinal Study of Aging (BLSA) and included 706 adults who were cognitively unimpaired at the time of biomarker measurement. These participants had a lower prevalence of heart ischemic disease (8.5%) and chronic kidney disease (23.7%) than that observed in U.S. adults over the age of 65 years (heart disease, 18.3%; chronic kidney disease, 33.7%), whereas the prevalence of heart failure (8.1%) was on par with the general population.
Researchers also included a cohort (n = 11,285) from the Atherosclerosis Risk in Communities (ARIC) study to determine whether proteomic indicators that were correlated with AD biomarkers predicted 25-year dementia risk. (Dark, 2023)
Greater protein-based risk for cardiovascular and kidney disease linked to AD biomarkers
The authors found that participants with proteomic results that indicated a higher risk for future kidney disease, cardiovascular events, and a heart failure prognosis risk were linked to lower concentrations of amyloid-beta and greater concentrations of p-tau181, NfL, and GFAP, even in individuals without clinically defined cardiovascular or kidney disease. Among participants with neuropathologically defined preclinical AD (as defined by PET scan), greater primary cardiovascular risk and heart failure prognosis were associated with higher levels of cortical amyloid-beta.
Notably, the kidney disease risk associations and cardiovascular disease risk and heart failure prognosis associations remained largely similar when participants with evidence of kidney dysfunction and cardiovascular disease were excluded.
Higher body fat percentage and visceral fat were associated with lower p-tau181, NfL, and GFAP, while greater lean body mass was associated with higher p-tau181 and lower NfL and GFAP. Among participants with a positive amyloid PET, poor heart failure prognosis was positively correlated with higher cortical amyloid beta, after adjusting for demographics.
In the ARIC study, a total of 2,063 (18.3%) had incident dementia over a median follow-up of 21.1 years. Increased dementia risk was associated with higher primary and secondary cardiovascular risk, as well as poorer heart failure prognosis, after adjustments for age, sex, race, study site, education, and APOE4 status.
The researchers acknowledged the study’s limitations. First, the proteomic health indicators were constructed and validated in cohorts that consisted primarily of white participants, and it's unclear whether they were optimal for the sizable subset of non-white participants in BLSA and ARIC. Additionally, the primary analyses were cross-sectional and could not shed light on how changing peripheral health might influence Alzheimer's biomarker progression. (Dark, 2023)
Sources:
Dark HE. (2023, October 6). Ann Neurol. Proteomic Indicators of Health Predict Alzheimer's Disease Biomarker Levels and Dementia Risk. https://pubmed.ncbi.nlm.nih.gov/37801487/
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