神経病理からみたAlzheimer病

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Significant neuropathological hallmarks of Alzheimer disease (AD) include amyloid–β (Aβ) deposition and the formation of associated senile plaques (SPs), concurrent with the appearance of neurofibrillary tangles (NFTs). Both SPs and NFTs are recognized more abundantly in AD brains than in the physiological range of normal aging. SPs are the extracellular deposits of Aβ, particularly abundant in the cerebral cortex. Based on the presence or absence of a dense Aβ core, plaques are morphologically classified as neuritic or diffuse, respectively. Composed of intraneuronal aggregates of hyperphosphorylated tau protein, NFTs are primarily formed in pyramidal cell neurons in the cerebral cortex. NFTs have a flame–like shape. Following the cell death, tangle–bearing neurons become extraneuronal “ghost” tangles. NFTs consist of abnormal 20 nm helical filaments with an 80 nm half–periodicity, termed paired helical filaments. The spatiotemporal progression of NFTs correlate with the severity of cognitive decline. The predictable progression of Aβ plaque pathology from the neocortex, over limbic structures, and basal ganglia to the brainstem and cerebellum is captured in phases described by Thal et al. Similarly, the progression of NFT pathology from the transentorhinal region to the limbic system and ultimately the neocortex has been described in stages proposed by Braak et al. Braak stages V and VI (isocortical stages) showed the strongest association with clinically observed dementia, while stages III and IV (limbic stages) were associated with mild cognitive impairment. Stages I and II (transentorhinal stages) were observed in asymptomatic individuals. The density of neuritic plaques was determined using the criteria defined by the Consortium to Establish a Registry for AD (CERAD). These staging systems are used internationally for the pathological diagnosis of AD according to the National Institute on Aging–Alzheimer's Association (NIA–AA) guidelines for the neuropathological assessment of AD. In these guidelines, each pathological hallmark is scored individually using a three–tiered scoring system, and these scores are used to assign the likelihood of AD pathology. In future aging and dementia studies, the significance of the neuropathological diagnosis of AD is expected to remain prominent.