Women Accumulate Alzheimer’s-Related Protein Faster

Summary: Study reports tau accumulation in the temporal lobe was 75% higher in women than men.

Source: Lund University

Alzheimer’s disease seems to progress faster in women than in men. The protein tau accumulates at a higher rate in women, according to research from Lund University in Sweden.

The study was recently published in Brain.

Over 30 million people suffer from Alzheimer’s disease worldwide, making it the most common form of dementia. Tau and beta-amyloid are two proteins known to aggregate and accumulate in the brain in patients with Alzheimer’s.

The first protein to aggregate in Alzheimer’s is beta-amyloid. Men and women are equally affected by the first disease stages, and the analysis did not show any differences in the accumulation of beta-amyloid. Memory dysfunction arises later, when tau starts to accumulate. More women than men are affected by memory problems due to Alzheimer’s, and it was for tau that the researchers found a higher rate of accumulation in women.

“Tau accumulation rates vary greatly between individuals of the same sex, but in the temporal lobe, which is affected in Alzheimer’s disease, we found a 75% higher accumulation rate in women as a group compared to men,” explains Ruben Smith, first author of the study.

The accumulation of tau is faster in patients who already have a pathological accumulation of beta-amyloid, and are in the early phase of the disease. The discovery that the accumulation rate of tau is higher in women remained even after adjusting for age and the levels of tau they had at the beginning. Together with data from three similar cohorts in the USA, the project contains 209 women and 210 men.

“The next step would be to examine why this accumulation is faster in women,” says Sebastian Palmqvist, the researcher responsible for the cognitive assessment of the patients.

The study did not investigate the reasons for the higher rate of tau accumulation in women.

“Our study strongly indicates that the faster spread of tau makes women more prone to develop dementia because of Alzheimer’s pathology compared to men. Future experimental studies will be important to understand the reasons behind this,” concludes Professor Oskar Hansson.

About this Alzheimer’s disease research news

Source: Lund University
Contact: Ruben Smith – Lund University
Image: The image is in the public domain

Original Research: Open access.
“The accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects” by Sebastian Palmqvist et al. Brain

Abstract

The accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects

The development of tau-PET allows paired helical filament tau pathology to be visualized in vivo. Increased knowledge about conditions affecting the rate of tau accumulation could guide the development of therapies halting the progression of Alzheimer’s disease. However, the factors modifying the rate of tau accumulation over time in Alzheimer’s disease are still largely unknown. Large-scale longitudinal cohort studies, adjusting for baseline tau load, are needed to establish such risk factors.

In the present longitudinal study, 419 participants from four cohorts in the USA (Avid 05e, n = 157; Expedition-3, n = 82; ADNI, n = 123) and Sweden (BioFINDER, n = 57) were scanned repeatedly with tau-PET. The study participants were cognitively unimpaired (n = 153), or patients with mild cognitive impairment (n = 139) or Alzheimer’s disease dementia (n = 127). Participants underwent two to four tau-PET (¹⁸F-flortaucipir) scans with a mean (± standard deviation) of 537 (±163) days between the first and last scan.

The change in tau-PET signal was estimated in temporal meta- and neocortical regions of interest. Subject specific tau-PET slopes were predicted simultaneously by age, sex, amyloid status (determined by amyloid-β PET), APOE ε4 genotype, study cohort, diagnosis and baseline tau load.

We found that accelerated increase in tau-PET signal was observed in amyloid-β-positive mild cognitive impairment (3.0 ± 5.3%) and Alzheimer’s disease dementia (2.9 ± 5.7%), respectively, when compared to either amyloid-β-negative cognitively unimpaired (0.4 ± 2.7%), amyloid-β-negative mild cognitive impairment (−0.4 ± 2.3%) or amyloid-β-positive cognitively unimpaired (1.2 ± 2.8%).

Tau-PET uptake was accelerated in females (temporal region of interest: t = 2.86, P = 0.005; neocortical region of interest: t = 2.90, P = 0.004), younger individuals (temporal region of interest: t = −2.49, P = 0.013), and individuals with higher baseline tau-PET signal (temporal region of interest: t = 3.83, P < 0.001; neocortical region of interest: t = 5.01, P < 0.001). Tau-PET slopes decreased with age in amyloid-β-positive subjects, but were stable by age in amyloid-β-negative subjects (age × amyloid-β status interaction: t = −2.39, P = 0.018).

There were no effects of study cohort or APOE ε4 positivity. In a similar analysis on longitudinal amyloid-β-PET (in ADNI subjects only, n = 639), we found significant associations between the rate of amyloid-β accumulation and APOE ε4 positivity, older age and baseline amyloid-β positivity, but no effect of sex. In conclusion, in this longitudinal PET study comprising four cohorts, we found that the tau accumulation rate is greater in females and younger amyloid-β-positive individuals, while amyloid-β accumulation is greater in APOE ε4 carriers and older individuals.

These findings are important considerations for the design of clinical trials, and might improve our understanding of factors associated with faster tau aggregation and spread.