2018 年 35 巻 3 号 p. 157-161
Suspected non–Alzheimer's disease (AD) pathophysiology (SNAP) is a biomarker–based concept that is defined as a condition characterized by normal levels of amyloid–β protein (Aβ) markers (A−), but abnormal neurodegeneration (or neuronal injury) markers (N+). Recent studies indicated that SNAP is found in 17–35% of individuals with mild cognitive impairment (MCI). Similarly, 7–39% of patients with clinically probable AD dementia are negative for Aβ. Progression of cognitive impairment in individuals with SNAP is slower than that in A+N+ subjects with high likelihood of AD pathophysiology. Pathological backgrounds of SNAP are heterogeneous, including non–AD neurodegeneration, cerebrovascular disorders, and mixed pathologies. Non–AD neurodegeneration would include primary age–related tauopathy (PART), which corresponds to senile dementia of the neurofibrillary tangle type (SD–NFT) (tangle–only dementia) at the stage of dementia, and argyrophilic grain disease. Pathogenesis of AD in older people would be more complex than previously recognized, in which widespread Aβ and tau pathologies may be commonly preceded by PART pathology in the medial temporal lobe. Further, current trials of disease–modifying therapies for AD are reviewed. In addition, the author refers to a preventive intervention against dementia/AD with polyphenols under development by his group.
