Pase MP, et al. - Researchers performed a cohort study of samples from 1,453 participants in the Framingham Heart Study and 367 individuals in the Memento study to investigate the utility of plasma total tau as a biomarker for dementia and related endophenotypes. Outcomes suggested a correlation of plasma total tau with endophenotypes of dementia and with the risk of incident clinical Alzheimer disease (AD) dementia, indicating the value of estimating plasma total tau for risk stratification and subsequent enrollment of high-risk individuals in dementia prevention trials.

Methods

• Researchers used data from the US community-based Framingham Heart Study with replication in the Memento study—a multicenter cohort of individuals with mild cognitive impairment or those with cognitive complaints recruited from memory clinics across France—to perform this prospective cohort study.
• Stored plasma samples in Framingham Heart Study participants during 2004 to 2011 were used to measure total tau levels.
• Individuals aged ≥ 65 years and dementia-free at baseline were follow-up for dementia for a median of 6 years.
• From Memento study participants, the investigators obtained plasma and/or cerebrospinal fluid samples from April 19, 2011, to June 22, 2016.
• Follow-up of dementia was done over a median of 4 years.
• From January to November 2018, they performed data analysis.
• Single-molecule array technology was used to measure plasma total tau level.
• They determined incidence of dementia of any cause (all dementia) and dementia due to clinical AD dementia as main outcomes and measures.

Results

• Overall dementia was reported in 134 patients in the Framingham sample; of these, 105 had AD dementia.
• After adjustment for age and sex, a 35% increase in AD dementia risk was observed in correlation with each SD unit increase in the log of plasma total tau level.
• Upon adding plasma total tau to a model including age and sex, they noted that stratification of participants for risk of AD dementia improved.
• They observed a correlation of higher plasma total tau level with poorer cognition across seven cognitive tasks (P < 0.05) and smaller hippocampi, as well as neurofibrillary tangles and microinfarcts at autopsy.
• In the replication cohort, they noted a weak correlation of plasma total tau level with cerebrospinal fluid total tau level; however, plasma total tau was at least as strongly correlated with incident AD dementia as cerebrospinal fluid total tau after adjustment for age and sex.