- Design
- Prospective single-centre memory-clinic cohort, 36 months
- Population
- 223 people with neurodegenerative or non-neurodegenerative cognitive impairment
- Primary outcome
- Change in plasma p-tau217 and NfL over 36 months
- Effect
- Steepest p-tau217 rise in AD with α-synuclein (2.19 pg/mL; p<0.001)
This single-centre memory-clinic cohort in Barcelona followed 223 people with cognitive impairment for 36 months. Diagnoses were set by CSF Alzheimer biomarkers and an α-synuclein seed amplification assay; plasma p-tau217 and neurofilament light were measured at baseline and three years.
Plasma p-tau217 rose fastest in Alzheimer disease with α-synuclein co-pathology, and remained stable in Lewy body dementia without Alzheimer pathology, frontotemporal dementia and non-neurodegenerative impairment. Neurofilament light was highest in frontotemporal dementia and in Alzheimer disease with α-synuclein.
This matters as blood biomarkers enter clinics: a rising p-tau217 tracks Alzheimer progression, and co-existing Lewy pathology appears to speed it. The α-synuclein-positive Alzheimer group was only 15 people, so this is a signal to watch rather than a basis for prognosis in an individual.
- Expect plasma p-tau217 to stay stable in frontotemporal and pure Lewy body dementia.
- Consider Lewy co-pathology when an Alzheimer patient declines faster than expected.
- Use neurofilament light as a marker of neuroaxonal injury, not of a specific disease.
- Do not use single biomarker values for individual prognosis yet.
Why it matters
Mixed pathology is common and may explain why some Alzheimer patients decline faster.
Don't overread it
Single centre and a 15-person key subgroup; this is hypothesis-generating.
The statistics, in plain English
The key subgroup had 15 patients, so the estimate of a faster rise is fragile. Mixed-effects models compare average trajectories between groups; they do not predict any one person's path.
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