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. 2025 Aug;45(4):e70011.
doi: 10.1111/neup.70011. Epub 2025 May 26.

Alzheimer's Disease With Cardiac Transthyretin Amyloidosis: A Clinicopathological Study of Autopsy Cases

Yasuo Sugita  1 , Takuya Furuta  2 , Kenji Takahashi  3 , Koichi Higaki  4 , Yoshiro Koda  5 , Shin-Ichiro Mori  6 , Shoko Hongo  7 , Hideomi Hamasaki  7 , Akiyoshi Kakita  7 , Mitsuharu Ueda  8 , Keisuke Kitagawa  8   9
Affiliations

Alzheimer's Disease With Cardiac Transthyretin Amyloidosis: A Clinicopathological Study of Autopsy Cases

Yasuo Sugita et al. Neuropathology. 2025 Aug.

Abstract

The relationship between Alzheimer's disease and cardiac transthyretin amyloidosis (ATTR) has been reported epidemiologically. However, the details of its clinicopathological characteristics are unclear. To clarify the pathogenesis of Alzheimer's disease combined with cardiac ATTR, 50 autopsy cases of Alzheimer's disease with cardiac hypertrophy were examined. Transthyretin amyloid deposition was studied by immunostaining in cases where amyloid deposition was suspected in various organs by HE staining. ATTR in systemic organs was also examined. The pathological diagnosis of Alzheimer's disease was done based on the National Institute on Aging and Alzheimer's Association (NIA-AA) guidelines. Cerebral amyloid angiopathy (CAA) was rated on a 3-point scale according to the Vonsattel scale. The pathological diagnosis of cardiac ATTR was done using a 3-point scale based on previously published findings on amyloid amounts. Six out of 50 patients were found to have cardiac ATTR by immunostaining and protein mass analysis of myocardial tissue. The sex distribution of the six patients was two males (Cases 3 and 6) and four females (Cases 1, 2, 4, and 5), and their ages were 97, 89, 91, 104, 86, and 77 years in Cases 1-6, respectively. In Cases 1-6, the NIAA score/CAA assessment/ATTR stages were intermediate/severe/G3, intermediate/moderate/G3, high/severe/G3, high/severe/G2, high/severe/G2, and intermediate/moderate/G2, respectively. Cases 1-5 also had cerebral infarction. In all cases, Transthyretin amyloid deposition was seen mainly in the vessel walls of various organs throughout the body. In the heart, transthyretin amyloid deposition was observed in the myocardial vessel walls and between myocardial fibers. On autopsy, cardiogenic cerebral infarction or heart failure was considered to be the main cause of death in Cases 1-5. These results indicate that Alzheimer's disease could be regarded as a systemic disease rather than just a localized disease presenting with dementia.

Keywords: Alzheimer's disease; amyloidosis; amyloid‐β; cardiac failure; cerebral infarction; transthyretin.

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References

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