Isolated elevation of 181p-tau in the cerebrospinal fluid is associated with distinct clinical features: Findings from a Danish memory clinic cohort

Abstract

Background

Deposition of amyloid-β and tau are key pathological events in Alzheimer's disease and may be assessed by cerebrospinal fluid (CSF) biomarkers. It remains uncertain whether patients who display abnormal phosphorylated tau in isolation differ from patients with other biomarker profiles.

Objective

The primary objective was to investigate differences in demographics, comorbidities, and cognitive performance in amyloid-β negative phosphorylated tau positive patients. Further, the aim was also to investigate the relationship between cognitive function and phosphorylated tau level.

Methods

A total of 1049 consecutive patients from the Copenhagen Memory Clinic Cohort from 2018 to August 2022 were included and divided into four groups based on the CSF biomarkers amyloid-β₄₂ (A) and phosphorylated tau (T). Data on co-morbidities, abuse, and neuropsychological tests were recorded, and retrospective data analyses were performed across all groups.

Results

A total of 2.8% participants had an A–T+ biomarker profile and were younger (Mean: 65.1 years, SD: 14.2), comprised of more men (65.5%) than the A + T– group and exhibited both more psychiatric illness (p = 0.027) and alcohol and/or drug abuse (p = 0.004) than the A + T+ group. The A–T+ group performed better on both Addenbrooke's Cognitive Examination (p = 0.002) and Mini-Mental State Examination (p = 0.001) as well as immediate (p = 0.026) and delayed recall (p = 0.009) compared to the A + T+ group but showed no difference compared to the A–T– group on all cognitive scores. Further, higher p-tau levels were associated with worse cognitive performance although effects were small.

Conclusions

The findings indicate that patients with the A–T+ biomarker profile have different clinical characteristic that may indicate a non-neurodegenerative background.