In a study of more than 1,700 adults, investigators found that imaging markers of cerebral amyloid angiopathy—a condition involving amyloid deposits in brain blood vessels—were associated with elevated Alzheimer’s disease–related plasma biomarkers and cognitive decline.
The investigators analyzed data from 1,708 individuals aged 45 years or older enrolled in a dementia registry across 25 hospitals in South Korea between 2016 and 2023. The participants were grouped by cognitive status: no impairment, mild impairment, or dementia of the Alzheimer type.
Imaging markers such as lobar cerebral microbleeds (CMB) and cortical superficial siderosis were linked to increased levels of three Alzheimer’s-related biomarkers: phosphorylated tau-217 (p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), which indicated tau pathology, astrocyte activation, and neuronal damage, respectively.
“The number of lobar CMBs was associated with increased p-tau217 levels ([beta] = 0.12, 95% confidence interval [CI] = 0.05–0.18), GFAP levels ([beta] = 0.07, 95% CI = 0.03–0.12), and NfL levels ([beta] = 0.07, 95% CI = 0.03–0.11),” said lead study author Sung Hoon Kang, MD, PhD, of the Department of Neurology at the Samsung Medical Center at the Sungkyunkwan University School of Medicine.
The presence of probable cerebral amyloid angiopathy (CAA), based on magnetic resonance imaging (MRI) using established diagnostic criteria, was also associated with elevated biomarker levels: p-tau217 (beta = 0.29), GFAP (beta = 0.20), and NfL (beta = 0.16).
Amyloid beta uptake in the brain, measured by positron emission tomography (PET), partially mediated these associations. For instance, amyloid beta uptake explained about 60% of the relationship between lobar CMBs and p-tau217. Similar mediation was observed in the associations between CAA and GFAP or NfL.
In contrast, vascular changes associated with hypertension—such as lacunes and deep CMBs—were linked only to NfL levels and were not mediated by amyloid beta uptake.
Cognitive outcomes were assessed in 1,381 participants who completed follow-up Mini-Mental State Examination (MMSE) tests. Higher lobar CMB counts in combination with elevated p-tau217 or GFAP levels were associated with faster annual MMSE decline. Lobar CMBs interacted with p-tau217 (beta = −0.56) and GFAP (beta = −0.44) to predict cognitive deterioration.
Plasma biomarkers were measured using high-sensitivity assays. Imaging assessments included MRI and amyloid PET. The analyses were adjusted for age, sex, body mass index, and APOE genotype. The findings were consistent across different cognitive subgroups.
Although the investigators focused on an Asian population, they noted that further research is needed in more diverse cohorts to improve generalizability. These findings may help identify individuals at increased risk for cognitive decline or adverse events when receiving amyloid-targeted therapies.
“Lobar cerebral microbleeds, in combination with [p-tau217] or [GFAP], were synergistically associated with cognitive changes,” the study authors concluded.
Full disclosures can be found in the study.
Source: JAMA Network Open
