Parkinson’s protein linked to faster Alzheimer’s progression in women
Alzheimer’s-related brain changes progressed up to 20 times faster in women who also had abnormal levels of a Parkinson’s-related protein, according to a Mayo Clinic study.
The findings suggest that when alpha-synuclein — a protein linked to Parkinson’s disease — accumulates alongside Alzheimer’s pathology, it may drive faster disease progression in women.
That interaction could help explain a long-standing disparity: women make up nearly two-thirds of people living with Alzheimer’s disease in the US.
“Recognising these sex-specific differences could help us design more targeted clinical trials and ultimately more personalized treatment strategies,” said Dr Kejal Kantarci, a Mayo Clinic neuroradiologist and senior author of the study.
Alzheimer’s disease is marked by the buildup of tau protein in the brain. Many people along the Alzheimer’s disease continuum also develop abnormal clumping of α-synuclein, a protein associated with Lewy body diseases such as Parkinson’s disease and dementia with Lewy bodies.
The researchers analysed data from 415 participants in the Alzheimer’s Disease Neuroimaging Initiative, a national research consortium that tracks brain changes over time. Participants underwent cerebrospinal fluid testing to detect abnormal α-synuclein and repeated brain imaging to measure changes in tau accumulation. About 17% of participants showed evidence of abnormal α-synuclein.
Among participants with both Alzheimer’s-related pathology and α-synuclein abnormalities, women accumulated tau dramatically faster than men with the same coexisting protein changes.
Elijah Mak, first author of the study and a Mayo Clinic neuroimaging researcher, commented: “This opens an entirely new direction for understanding why women bear a disproportionate burden of dementia. If we can unravel the mechanisms behind this vulnerability, we may uncover targets we haven’t considered before.”
The researchers are now examining whether these sex-specific effects also appear in patients with dementia with Lewy bodies, where α-synuclein is the primary disease driver rather than a coexisting pathology.