期刊
TRENDS IN NEUROSCIENCES
卷 38, 期 10, 页码 621-636出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tins.2015.08.006
关键词
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资金
- National Institutes of Health [AG030209, AG15799, AG033914]
- Alzheimer's Association
- American Federation for Aging Research (AFAR)
- Bright Focus
Studies of Alzheimer's disease (AD) have predominantly focused on two major pathologies: amyloid-beta (A beta) and hyperphosphorylated tau. These misfolded proteins can accumulate asymptomatically in distinct regions over decades. However, significant AD accumulation can be seen in individuals who do not develop dementia, and tau pathology limited to the transentorhinal cortex, which can appear early in adulthood, is usually clinically silent. Thus, an interaction between these pathologies appears to be necessary to initiate and propel disease forward to widespread circuits. Recent multidisciplinary findings strongly suggest that the third factor required for disease progression is an aberrant microglial immune response. This response may initially be beneficial; however, a maladaptive microglial response eventually develops, fueling a feed-forward spread of tau and AD pathology.
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