Transthyretin amyloid deposits in the heart were found in 12% of patients with Alzheimer’s disease and thickened heart muscle, suggesting that cardiac transthyretin amyloidosis (ATTR-CM) may be an underrecognized contributor to death in older adults with dementia, according to a study published recently in Neuropathology.
“Alzheimer’s disease should be regarded as a systemic disease rather than just a localized disease presenting with dementia,” said the study’s authors.
What is transthyretin?
Transthyretin (TTR) is a transport protein produced in the liver. Its role is to carry vitamin A (retinol) and thyroxine, a thyroid hormone, around the body. In ATTR-CM, it is faulty or unstable, causing it to misfold and become deposited in the heart, nerves and other internal organs.
In this study of 50 autopsy cases of patients with Alzheimer’s disease and cardiac hypertrophy, six were confirmed to have ATTR-CM through immunostaining and protein mass analysis. These six patients, aged 77 to 104, included four women and two men. Five of the six also had strokes or heart failure listed as the likely cause of death, indicating that ATTR-CM may have played a direct role in their final outcomes.
Transthyretin amyloid deposits were found not only in the heart, specifically in blood vessel walls and between heart muscle fibers, but also in other organs throughout the body. However, these deposits were not observed in the brain, including the meninges, cerebral vessels, or plaques, reinforcing that the cardiac and systemic amyloid was distinct from the brain changes seen in Alzheimer’s itself.
Read more about ATTR-CM signs and symptoms
This study followed Alzheimer’s pathology guidelines from the National Institute on Aging and Alzheimer’s Association. Three of the six cases of ATTR-CM had intermediate-level Alzheimer’s, and three had high-level Alzheimer’s disease. The extent of cardiac ATTR ranged from moderate to severe. All six had no known family history of amyloidosis or symptoms of nerve damage, pointing to wild-type ATTR-CM, the form commonly linked to aging.
Cerebral amyloid angiopathy, a form of vascular amyloid buildup in the brain, was also common in the full study population, appearing in over half of cases. Still, in the ATTR-CM group, death was primarily due to heart-related issues, not cognitive decline alone.
These results show that Alzheimer’s disease may not be limited to the brain but rather be part of a broader systemic condition affecting multiple organs, raising awareness that ATTR-CM may coexist with Alzheimer’s disease in elderly individuals and contribute to fatal events such as stroke or heart failure. Recognizing this overlap could help physicians manage cardiovascular risks in older adults with dementia and improve planning for end-of-life care.
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