Cleveland Clinic Research Shows Strong Link Between Lewy Body Pathology and Brain Bleeds in Patients with Alzheimer’s Disease

New Cleveland Clinic research found the presence of Lewy body pathology – abnormal aggregations of the proteins alpha-synuclein and neurites in the brain – in association with Alzheimer’s disease greatly increased the risk for cerebral amyloid angiopathy, or brain bleeds.

Published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the findings suggest identifying risk factors for cerebral amyloid angiopathy is important for assessing patient candidacy for emerging anti-amyloid therapies to treat mild Alzheimer’s.

“Currently, commonly tested biomarkers of Alzheimer’s do not enable the clinician to rule out co-pathologies that increase risk for cerebral amyloid angiopathy,” said Jagan Pillai, M.D., Ph.D., a neurologist at Cleveland Clinic’s Lou Ruvo Center for Brain Health in Cleveland and lead author of the study. “These findings provide further clues about underlying pathologic processes and should be considered when assessing a patient for anti-amyloid therapies.”

Cerebral amyloid angiopathy is associated with abnormal deposits of amyloid protein in cerebral blood vessels. As new anti-amyloid therapies target amyloid protein, there is an elevated risk of complications like brain bleed and stroke in patients undergoing treatment for mild cognitive impairment or early Alzheimer’s. Detecting factors that predict cerebral amyloid angiopathy can therefore help determine if a patient is a good candidate for the therapy.

The retrospective study looked at brain autopsy results from more than 2,300 people who had Alzheimer’s, Lewy body dementia or both, and found that cerebral amyloid angiopathy was present in:

• 82% of Alzheimer’s-Lewy body pathology cases
• 78% of Alzheimer’s cases
• 41% of Lewy body pathology cases

In addition, known genetic risk for Alzheimer’s disease, APOE4, was associated with increased risk of cerebral amyloid angiopathy in all dementia groups, but highest in the Lewy body pathology group.

These findings provide further impetus to evaluate the role for biomarkers to detect these additional pathologies accurately in patients to enable better clinical decision-making around anti-amyloid therapies for Alzheimer’s patients. Identifying Lewy body pathology and APOE ε4 status may prove vital in assessing risk and avoiding potential complications, particularly in younger patients, where typical clinical symptoms of underlying Lewy body pathology may not yet be noted.