Neurology

Plasma p-tau217 “clock” predicts age of Alzheimer’s symptom onset within a few years

Longitudinal plasma %p-tau217 data from two cognitively unimpaired cohorts (n=258 and n=345) were used to construct biomarker clock models. The estimated age at %p-tau217 positivity correlated with age at symptomatic Alzheimer’s onset, with adjusted R² values up to 0.612. Median absolute error for onset prediction was 3.0–3.7 years, suggesting clinically meaningful temporal precision for trial enrichment and counseling. Older individuals had a shorter interval between %p-tau217 positivity and symptom onset, indicating age-dependent preclinical windows. 1

Plasma AT(N) biomarkers distinguish Alzheimer’s disease and FTLD in a diverse Latin American cohort

In a multinational Latin American cohort of 605 individuals, plasma Aβ42/40, p-tau217, p-tau181, and NfL differentiated Alzheimer’s disease and FTLD from controls. Both disorders showed reduced Aβ42/40 and elevated p-tau and NfL, with larger NfL increases in FTLD, reflecting greater axonal injury. Plasma biomarker models achieved ROC AUCs of 0.83 for Alzheimer’s disease and 0.88 for FTLD. Adding neuroimaging and cognitive measures increased diagnostic accuracy to AUC 0.89 for Alzheimer’s disease and 0.95 for FTLD. 2

Subvoxel QSM MRI separates PD and MSA by quantifying α-synuclein–related susceptibility and iron

This prospective study applied subvoxel quantitative susceptibility mapping in 273 participants: 107 Parkinson disease, 62 multiple system atrophy, and 104 healthy controls. Substantia nigra pars compacta in synucleinopathies showed increased diamagnetic signal consistent with α-syn aggregation and higher paramagnetic signal indicating iron deposition versus controls. MSA demonstrated more widespread QSM abnormalities, which correlated with symptom severity (correlation coefficients greater than 0.26). QSM measures differentiated Parkinson disease from controls (AUC 0.87), MSA from controls (AUC 0.94), and Parkinson disease from MSA (AUC 0.96). 3

IL-6 and hsCRP signal higher poststroke vascular risk regardless of atrial fibrillation status

An individual participant data meta-analysis pooled 11 prospective studies including 10,080 ischemic stroke patients, 2,134 with atrial fibrillation. Patients with atrial fibrillation had higher inflammatory markers, persisting beyond the acute phase and independent of stroke severity and sampling time. Higher hsCRP was associated with increased major adverse cardiovascular events in both atrial fibrillation and non–atrial fibrillation patients, without interaction by rhythm status. hsCRP did not clearly predict recurrent stroke alone, whereas IL-6 was associated with both recurrent stroke and major events across groups. 4