Genetically proxied blood pressure, vascular brain injury, and Alzheimer's disease pathology

Aug 28, 2025Alzheimer's & dementia : the journal of the Alzheimer's Association

Blood pressure genes linked to blood vessel brain damage and Alzheimer's disease changes

AI simplified

Alzheimers & Treatments on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Genetically proxied lower systolic blood pressure is associated with reduced risk of all vascular brain injury measures.

Lower systolic blood pressure correlates with a decrease in atherosclerosis, arteriolosclerosis, gross infarcts, and microinfarcts.
No associations were found between systolic blood pressure and Alzheimer's disease pathology, including amyloid and tau measures.
Diastolic blood pressure analyses showed similar results to those of systolic blood pressure.
These findings indicate that lowering blood pressure may protect against dementia primarily by reducing vascular brain injury rather than directly influencing Alzheimer's disease.

AI simplified

INTRODUCTION: Lower blood pressure (BP) is linked to reduced dementia risk, though it is uncertain whether this benefit stems solely from mitigating vascular brain injury (VBI) or also extends to directly influencing Alzheimer's disease (AD) pathology. We leveraged Mendelian randomization (MR) to assess whether lifelong lower BP is causally associated with neuropathological correlates of VBI and AD.

METHODS: We identified genetic proxies for systolic and diastolic BP (n = 1,028,980) and applied them in MR analyses of post mortem neuropathological measures of VBI and AD (n = 6363-7786).

RESULTS: Genetically proxied lower systolic BP associated with reduced risk of all VBI measures, including atherosclerosis, arteriolosclerosis, gross infarcts, and microinfarcts. There was no evidence for associations between systolic BP and AD pathology, including measures of amyloid and tau pathology. Diastolic BP analyses yielded similar results.

DISCUSSION: These findings suggest that BP-lowering protects against dementia by mitigating VBI rather than by directly affecting AD pathology.

HIGHLIGHTS: It is uncertain whether blood pressure impacts dementia risk solely through its effects on blood vessel health, or whether it also impacts Alzheimer's disease (AD) pathology. We performed a Mendelian randomization study using genetic predictors of blood pressure applied to a unique autopsy study of neuropathological correlates of both vascular brain injury and AD pathology. We found evidence that genetically lowered blood pressure solely impacts vascular brain injury, with no effects on AD pathology.

Full Text

Full text is available at the source.

View full text ↗

Genetically proxied blood pressure, vascular brain injury, and Alzheimer's disease pathology

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the alzheimers & treatments brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the alzheimers & treatments brief