Alzheimer’s Blood Biomarkers Linked to Early Cognitive Differences Before Dementia

Blood-based screening for Alzheimer’s disease offers a noninvasive, lower-cost alternative to brain imaging or spinal fluid testing, yet its ability to flag the earliest cognitive changes has been unclear. Because Alzheimer’s pathology begins years before symptoms, identifying subtle decline in midlife could inform care. Determining whether plasma biomarkers align with early cognitive differences is therefore clinically important. A new study shows that tau- and amyloid-based blood measures in adults aged 53–69 without dementia correlate with lower baseline performance and higher risk of rapid decline.

At the University of California, San Francisco (UCSF), investigators evaluated blood biomarkers for Alzheimer’s disease in a community cohort of midlife adults without dementia. The approach quantified tau and amyloid plaque proteins in plasma and examined their relationship to neurocognitive performance. The findings, published May 28, 2026, in The Lancet, address whether circulating markers of hallmark Alzheimer’s pathology align with subtle cognitive differences before clinical diagnosis.

Image: The study addressed whether circulating markers of hallmark Alzheimer’s pathology align with subtle cognitive differences before clinical diagnosis (image credit: Adobe Stock)

The study analyzed 1,350 participants aged 53 to 69 from the multisite CARDIA study. Six percent of participants had high levels of both amyloid and tau in blood. At baseline, this high-biomarker group performed worse on processing speed and executive function tasks.

Longitudinal testing five years later showed prognostic value of the biomarkers. Participants with high amyloid and tau had about 2.5 to 4 times the risk of rapid decline in verbal memory and around 3 to 4 times the risk of rapid decline in processing speed. The cohort was 58% women and 45% Black, with the remainder white.

UCSF researchers noted that blood tests are inexpensive and noninvasive compared with scans or cerebrospinal fluid assays, but emphasized careful interpretation. They highlighted that such tests pertain to Alzheimer’s pathology and not other dementias and cautioned about the possibility of false positives. Collectively, the results suggest that specific plasma measures of tau and amyloid in midlife adults without dementia align with early cognitive differences and forecast faster decline in select domains.

“Alzheimer’s disease pathology begins years before symptoms emerge. Detecting the disease early means patients can target modifiable risk factors and maybe seek other care,” said Kristine Yaffe, MD, vice chair in the UCSF Department of Psychiatry and Behavioral Sciences.

“There’s a possibility of false positives and they can only be used for Alzheimer’s, not other dementias, meaning about 60% to 70% of all dementia cases. But for some people who discover they have the biomarkers, testing could open a window to embark on interventions that may postpone Alzheimer’s onset,” said Yaffe