Recent advances in neuropathological research on Alzheimer disease and Lewy body disease

Abstract

A definitive diagnosis of neurodegenerative diseases, including Alzheimer disease (AD) and Lewy body disease (LBD), requires a neuropathological examination. Each neurodegenerative disease affects specific vulnerable regions and is associated with system degeneration, characterized by the accumulation of abnormal proteins and the formation of distinctive morphological aggregates in the nerve and glial cells, called proteinopathy.

The neuropathological findings of AD are characterized by the appearance of neurofibrillary tangles (NFTs) and senile plaques. The likelihood of pathological AD is determined by a comprehensive assessment of the spread of amyloid β (Aβ), the density of senile plaques, and the distribution of NFTs. The pathological hallmark of AD is the presence of AD–related pathology beyond the physiological range. Appropriate evaluation should be performed according to standardized protocols for neuropathological diagnosis.

LBD refers to conditions in which Lewy bodies are pathologically recognized as a disease concept. Lewy bodies appear widely not only in the brain but also in the peripheral autonomic nervous system, making LBD a systemic disease. The extent and severity caused by Lewy body involvement vary by case, and the affected system corresponds to various clinical symptoms. The pathological diagnosis of dementia with Lewy bodies (DLB) is based on the international diagnostic criteria of the DLB Consortium. LBD pathology often coexists with AD pathology, and the likelihood of detecting pathological findings of both diseases increases with age.

To enhance the sensitivity of clinical diagnosis of AD and LBD and clarify their pathogeneses, comparing and examining the clinical findings and neuropathological observations in detail in each case is crucial.