Blood Test Detects Alzheimer’s Pathology in Other Clinical Syndromes

  • Plasma p-tau217 successfully identified Alzheimer’s pathology in several neurodegenerative syndromes.
  • This included disorders not typically associated with Alzheimer’s disease, like frontotemporal dementia.
  • Alzheimer’s pathology in syndromes related to frontotemporal lobar degeneration correlated with worse cognitive performance.

A blood test identified clinically relevant Alzheimer’s disease pathology in several clinical syndromes, a clinicopathological study showed.

Plasma phosphorylated tau 217 (p-tau217) detected Alzheimer’s pathology across neurodegenerative syndromes with an area under the receiver operating characteristic curve (AUC) of 0.95, reported Lawren VandeVrede, MD, PhD, of the University of California San Francisco (UCSF), and co-authors in JAMA Neurology.

The blood-based biomarker performed slightly better in Alzheimer’s-related syndromes (AUC 0.98, 95% CI 0.95-1.00) than in frontotemporal lobar degeneration (FTLD)-related syndromes (AUC 0.89, 95% CI 0.83-0.94).

At autopsy, Alzheimer’s neuropathology was seen in 88% of decedents with Alzheimer’s-related syndromes and 23% of decedents with FTLD-related syndromes, the researchers said. In 15% of people with FTLD-related syndromes, Alzheimer’s disease was considered a co-pathology.

The presence of Alzheimer’s in FTLD-related syndromes was associated with lower Mini-Mental State Examination scores (mean worsening of 2.9 points on the 30-point scale, P<0.05), worse performance on memory, executive, and visuospatial composites, and increased rates of posterior cortical atrophy, the researchers added.

The study used gold-standard autopsy confirmation to show that a blood test for Alzheimer’s disease accurately detected amyloid plaques and tau tangles across several clinical syndromes, including those not typically associated with Alzheimer’s disease like frontotemporal dementia, VandeVrede said.

“This means a clinician ordering an Alzheimer’s disease blood test can have high confidence the result is detecting the presence of plaques and tangles — even in atypical or unusual presentations — but it’s important to consider the clinical presentation as Alzheimer’s may not be the only cause of the patient’s symptoms,” he told MedPage Today.

Because this study shows that blood tests can detect clinically relevant Alzheimer’s pathology, it provides support for evaluating Alzheimer’s-targeting treatments in patients not currently included in Alzheimer’s drug trials, he added.

Whether clinically available Alzheimer’s blood-based tests have value in FTLD-related syndromes isn’t clear, the researchers noted. Work linking Alzheimer’s co-pathology with FTLD syndromes has been limited because they require autopsy data due to a lack of confirmatory biomarkers in FTLD.

VandeVrede and co-authors studied 349 autopsied individuals who had both clinical evaluations and neuropathological examinations at the UCSF Alzheimer Disease Research Center from 2008 to 2021. About half (55%) were male, and mean age at death was 72.

Overall, 125 people had been diagnosed with clinical syndromes related to Alzheimer’s disease; 198 people had a clinical diagnosis supporting FTLD, and 16 people were cognitively unimpaired at the time of evaluation.

Of people with FTLD-related syndromes, 76 had behavioral variant frontotemporal dementia, 40 had progressive supranuclear palsy-Richardson syndrome, 35 had corticobasal syndrome, 21 had nonfluent variant primary progressive aphasia (PPA), and 21 had semantic variant PPA.

Outcomes involved three plasma biomarkers: p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Alzheimer’s disease was defined as intermediate or high Alzheimer’s neuropathological change (ADNC) at autopsy.

Neuropathological stage at autopsy was higher in Alzheimer’s-related syndromes; 93% of these participants had high ADNC compared with 56% of people with FTLD. Plasma p-tau217 concentrations were higher in Alzheimer’s-related syndromes (mean 0.28 pg/mL) than in FTLD-related syndromes (mean 0.10 pg/mL; P<0.05).

Both NfL (AUC 0.73, 95% CI 0.68-0.78) and GFAP (AUC 0.75, 95% CI 0.67-0.80) had lower performance for detecting Alzheimer’s pathology. These plasma markers had little to no diagnostic value, either alone or in combination with p-tau217, the researchers said.

An important limitation was that clinical features and plasma concentrations were compared with autopsy findings at varying intervals, sometimes spanning several years between assessments, the researchers acknowledged.

“Our analyses controlled for interval to autopsy, but it is not possible to know whether the neuropathology on which autopsy diagnoses are based was present at the time of assessment or developed afterwards,” VandeVrede and co-authors wrote. In addition, the cohort may represent a biased sample since the UCSF center specializes in atypical Alzheimer’s- and FTLD-associated neurodegeneration.

  • Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

VandeVrede was funded by grants from the National Institutes of Health, the American Academy of Neurology, the Alzheimer’s Association, and the Shenandoah Foundation. He reported nonfinancial support from Biogen (site principal investigator for Biogen-sponsored clinical trial) outside the submitted work.

Co-authors were supported by several nonprofit and academic groups, and reported relationships with industry.

Primary Source

JAMA Neurology

Source Reference: VandeVrede L, et al “Detection of Alzheimer neuropathology in Alzheimer and non-Alzheimer clinical syndromes with blood-based biomarkers” JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2024.5017.

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