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SearchFindings offer important implications for screening candidates for new Alzheimer’s disease treatments
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:
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.
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation, Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognized in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 83,000 employees worldwide are more than 6,600 salaried physicians and researchers, and 21,900 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,725-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, 300 outpatient facilities, including locations in northeast Ohio; Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2025, there were 15.9 million outpatient encounters, 343,000 hospital admissions and observations, and 336,000 surgeries and procedures throughout Cleveland Clinic’s health system. Visit us at clevelandclinic.org. Follow us at x.com/CleClinicNews. News and resources are available at newsroom.clevelandclinic.org.
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