The occurrence range of proper lesions (neurofibrillary tangles and senile plaques) to Alzheimer’s disease : patho-anatomical study of a familial Alzheimer

AD is a rapidly increasing dementia whose measure for medical and social welfare has been a serious social problem in Japan. The brain lesions of AD are characterized by 3 main histological changes: NFT, SP, and loss of neurons. With the reexamination of an AD case with a 25 year-clinical course as an opportunity, the author revealed the maximal range of occurrence of NFT and SP in AD. The results showed that neurons were classi›ed into 3 types: neuron types with NFT-rich, NFT-rare, and NFT-free. As to the pathogenesis of AD brain lesions, it is known that Aβ deposition occurs first and the oligomers with the highest toxicity develop into proto›brils and ›brils and ›nally form neuritic plaques which contain degenerated neurites. In addition, Aβ oligomers generated in and around synapses and inside neurons are considered to induce cell death due to the toxicity to neurons and glial cells. On the other hand, it is believed that by GSK3β which is activated by the overproduction of Aβ inside neurons, hyperphosphorylation of tau proceeds and soluble oligomers of tau polymerize to be insoluble granular aggregates, and then become larger insoluble NFT. It is still unclear where tau oligomers or granules associate with Aβ oligomers or proto›brils to develop NFT and Aβ ›brils, respectively, and what mechanisms play roles to develop NFT in “NFT only tauopathies”. Detailed analyses that reveal all of differences between NFT-rich and NFT-free neurons may open a road to pathogenetic mechanisms of NFT formation.

弘前医療福祉大学紀要, 2(1), 2011, p.1-14