BY LIZETTE BORRELI
Women are more likely to show Alzheimer's disease (AD) pathophysiology, a series of recent studies have shown. Now, an analysis of cross-sectional data, published online on February 4 in JAMA Neurology, provides further support for the theory that women develop more tau pathology than men.
In a study of two cross-sectional cohorts of clinically normal adults, women with a higher amyloid burden showed a higher tau signal in their entorhinal cortices than men.
"These findings lend support to a growing body of literature that highlights a biological underpinning for sex differences in Alzheimer disease risk," Rachel F. Buckley, PhD, a research fellow in neurology at Massachusetts General Hospital in Boston, and her colleagues, wrote.
A 2018 meta-analysis published in JAMA Neurology reported greater cerebrospinal fluid (CSF) total and phosphorylated tau in female apolipoprotein E (APOE) ε4 carriers than male carriers with the findings influenced by abnormal levels of amyloid-beta.
However, sex differences in amyloid-beta burden alone have not been reported in older adults, and studies have not yet explored these differences in regional tau deposition related to amyloid-beta burden and APOE ε4, according to the researchers.
To observe sex differences in the cross-sectional relationship between amyloid-beta and regional tau deposition as measured with positron emission tomography (PET), the team evaluated the Harvard Aging Brain study (HABS) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), both comprising clinically normal individuals, who received both tau and amyloid-beta PET scans from January 2016 to February 2018.
The HABS cohort included 193 individuals (average age, 74 years; 62 percent women) who had carbon 11–labeled Pittsburgh Compound B (PIB) PET to assess amyloid-beta. The ADNI cohort included 103 individuals (average age 76; 51 percent women) who underwent florbetapir PET to assess amyloid beta. Both the HABS and ADNI cohort had tau assessed with flortaucipir F18 PET.
Among both cohorts, the average Mini-Mental State Examination Score (MMSE) in each group was about 29 points out of 30 maximum points on the scale.
The researchers collected a blood sample in each study for direct genotyping of APOE.
The findings revealed the HABS cohort performed significantly better on logical memory (delayed recall) than the ADHI group, but did not differ by age, sex, amyloid positivity, or APOE ε4 status.
In the HABS group, women were younger (average age 73) compared to those in the ADNI group (average age 75).
Among amyloid-positive individuals, women had more tau signal in their entorhinal cortices than men (p=.02). This became more evident as the presence of amyloid increased. Higher amyloid-burden led women to have higher entorhinal cortex tau than men in both the HABS (p=.04) and the ADNI cohorts (p value?)
Sex and the presence of APOE did not appear to influence tau deposition in the HABS group. However, in the ADNI group, the interaction between sex and APOE ε4 was spotted in a meta-region that included the entorhinal cortex, inferior temporal cortex, amygdala, fusiform gyrus, and the parahippocampal cortex, with the association stronger among women than men.
Overall, clinically normal women showed higher regional tau compared to men, especially women with higher amyloid-beta burden, specifically seen in the entorhinal cortices.
Study limitations included using cohort samples—the ADNI group was older, had lower memory performance, and were more likely to have an advanced preclinical AD trajectory—compared with the HABS group. Moreover, both groups experienced different assessments of amyloid-beta.
Dr. Buckley is funded with the National Health and Medical Research Council Dementia Research Fellowship (APP1105576). Other researchers reported relationships with Eli Lilly, Biogen, Cortexyme, the European Union's Horizon 2020 Research and Innovation Programme, Janssen Pharmaceuticals, Lundbeck Pharmaceuticals, Bayer, GE Healthcare, Siemens Medical Solutions, Sanofi Genzyme, Novartis, Roche, Ionis Pharmaceuticals, AZTherapies, Lundberg, AbbVie, Navidea, Bracket, Avid Radiopharmaceuticals, Fidelity Biosciences, Harvard NeuroDiscovery Center, and the Alzheimer's Association.
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Buckley RF, Mormino EC, Rabin JS, et al. "Sex differences in the association of global amyloid and regional tau deposition measured by positron emission tomography in clinically normal older adults." JAMA Neurol 2019; Epub 2019 Feb 4.