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Blood-based biomarkers may help differentiate people with different dementias and monitor disease changes over time, a longitudinal study showed.

Plasma markers showed different profiles in Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and progressive supranuclear palsy, reported Leonidas Chouliaras, PhD, of the University of Cambridge in England, and co-authors in the .

Among 300 older adults, neurofilament light (NfL) was elevated in all people with dementias compared with controls. In addition:

• Phosphorylated tau at threonine 181 (p-tau181) was elevated in a group of people with amyloid-positive mild cognitive impairment or Alzheimer's dementia, compared with all other groups
• Amyloid beta (Aβ) ratio Aβ42/40 was lower in the Alzheimer's group compared with controls and those with frontotemporal dementia
• Glial fibrillar acid protein (GFAP) was elevated in the Alzheimer's group and in Lewy body dementia
• P-tau181 and GFAP correlated with longitudinal cognitive decline in the Alzheimer's group, after adjusting for age and sex

A new matrix -- blood -- is "changing the way we approach biomarkers in neurological diseases," observed Lucilla Parnetti, MD, PhD, of the University of Perugia in Italy, and co-authors in an .

Blood Aβ42/Aβ40 and p-tau181 reflect amyloidosis and tauopathy in Alzheimer's disease with reliability similar to that of cerebrospinal fluid (CSF), Parnetti and colleagues pointed out. "Also, ongoing neurodegeneration and neuroinflammation can be efficiently quantified by blood NfL and GFAP, respectively," they wrote.

"The non-invasiveness of blood sampling is the main benefit of plasma over CSF, which makes blood-based biomarkers easily repeatable along time as outcome measure for disease-modifying treatments," the editorialists added.

In their study, Chouliaras and colleagues measured plasma biomarkers of 63 people with amyloid-positive mild cognitive impairment or Alzheimer's dementia, 117 people with Lewy body dementia, 28 people with frontotemporal dementia, 19 people with progressive supranuclear palsy, and 73 dementia-free controls in cohorts recruited from U.K. National Health Service memory clinics. People with Lewy body dementia had known PET amyloid status.

Participants had clinical exams with cognitive and neuropsychiatric assessments at baseline, which were repeated annually for up to 3 years, depending on the cohort. Cognitive function was measured using the , revised version. Plasma biomarkers were measured once, at baseline, using single molecule immunoassays.

Baseline mean ages ranged from 64.5 in the frontotemporal dementia group to 75.6 in people with Lewy body dementia. Age was associated with p-tau181, NfL, and GFAP levels, but not Αβ42/40. Sex was not associated with significant differences in biomarker levels.

For diagnostic accuracy, the best performances were achieved in distinguishing Alzheimer's from frontotemporal dementia, with p-tau181 showing an area under the curve (AUC) of 0.88, those with Aβ42/Aβ40 showing an AUC of 0.88, those with NfL showing an AUC of 0.85, and those with GFAP showing an AUC of 0.84. None of these biomarkers, however, could discriminate Alzheimer's from Lewy body dementia.

When PET amyloid-positive and amyloid-negative cases of Lewy body dementia were compared, no differences in p-tau181, Αβ42/40, NfL, or GFAP plasma levels were seen. This finding suggesting p-tau181 could identify Alzheimer's co-pathology in Lewy body dementia, but that study used CSF Aβ42/40 and PET tau instead of PET amyloid, Chouliaras and co-authors noted.

The study had several limitations, the researchers acknowledged. It lacked CSF, PET, or postmortem confirmation of diagnosis for all participants, and it's likely some clinical diagnoses involved mixed or alternative pathologies.

"In addition, we had a single biomarker assessment at baseline, so we cannot determine how change in biomarkers over time varies between the different disorders," Chouliaras and co-authors wrote. Future studies need to validate findings of elevated plasma markers in Lewy body disease, frontotemporal dementia, and progressive supranuclear palsy and test levels of p-tau217 and p-tau231, they added.

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