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Concurrent cardiac transthyretin and brain β amyloid accumulation among the older adults: The Hisayama study
Hideomi Hamasaki1, Masahiro Shijo1,2, Ayaka Nakamura1
1Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Insights
Alzheimer's disease brain pathology correlates with cardiac transthyretin amyloid (ATTR) deposition in individuals aged 90 and younger. This finding highlights a link between neurodegenerative and cardiovascular changes in older adults.
Area of Science:
- Neuropathology
- Cardiovascular Pathology
- Aging Research
Background:
- Cognitive impairment is linked to cardiovascular diseases.
- Alzheimer's disease (AD) and cardiac transthyretin amyloid (ATTR) deposition are age-related conditions.
- Investigating the interplay between brain and heart pathologies is crucial for understanding aging and dementia.
Purpose of the Study:
- To examine the relationship between Alzheimer's disease pathologies in the brain and cardiac ATTR deposition.
- To assess the correlation between cerebral amyloid angiopathy (CAA), cardiac fibrosis, and AD pathologies.
- To determine if age influences the association between cardiac ATTR deposition and AD brain pathology.
Main Methods:
- Analysis of 240 autopsy cases from a Japanese population-based study.
- Immunohistochemical detection and grading of brain Aβ, tau protein, and cardiac ATTR.
- Grading of cerebral amyloid angiopathy (CAA) and quantification of cardiac fibrosis.
Main Results:
- Cardiac ATTR deposition increased with age, particularly after 75 years.
- ATTR deposition was more prevalent and severe in dementia cases.
- A significant correlation was found between cardiac ATTR deposition and AD brain pathologies (Aβ phase, CERAD score, Braak stage) in individuals aged ≤90 years.
- No significant correlation was observed between cardiac ATTR deposition and CAA, or between cardiac fibrosis and AD pathologies.
Conclusions:
- Alzheimer's disease brain pathology is associated with cardiac ATTR deposition in individuals aged 90 years or younger.
- The findings suggest a potential link between specific neurodegenerative and cardiovascular changes in this age group.
- Further research is needed to elucidate the mechanisms underlying this association and its clinical implications.
Abstract:
Previous studies have revealed risk for cognitive impairment in cardiovascular diseases. We investigated the relationship between degenerative changes of the brain and heart, with reference to Alzheimer's disease (AD) pathologies, cardiac transthyretin amyloid (ATTR) deposition, and cardiac fibrosis. A total of 240 consecutive autopsy cases of a Japanese population-based study were examined. β amyloid (Aβ) of senile plaques, phosphorylated tau protein of neurofibrillary tangles, and ATTR in the hearts were immunohistochemically detected and graded according to the NIH-AA guideline for AD pathology and as Tanskanen reported, respectively. Cerebral amyloid angiopathy (CAA) was graded according to the Vonsattel scale. Cardiac fibrosis was detected by picrosirius red staining, followed by image analysis. Cardiac ATTR deposition occurred after age 75 years and increased in an age-dependent manner. ATTR deposition was more common, and of higher grades, in the dementia cases. We subdivided the cases into two age groups: ≤90 years old (n = 173) and >90 years old (n = 67), which was the mean and median age at death of the AD cases. When adjusted for age and sex, TTR deposition grades correlated with Aβ phase score (A2-3), the Consortium to Establish a Registry for AD score (sparse to frequent), and high Braak stage (V-VI) only in those aged ≤90 years at death. No significant correlation was observed between the cardiac ATTR deposition and CAA stages, or between cardiac fibrosis and AD pathologies. Collectively, AD brain pathology correlated with cardiac TTR deposition among the older adults ≤90 years.
