phagocytotic function in vivo and in vitro, and expression of the ABCA7 gene is regulated by cell cholesterol mainly through the SRE/SREBP system in a negative feed-back fashion in contrast to positive feedback by the LXR/RXR system for ABCA1. ABCA7 thus links cholesterol metabolism to host defense system. Clinical significance In 2011, two genome-wide association studies (GWAS) identified ABCA7 as a new susceptibility locus for late-onset Alzheimer's disease. The finding was also confirmed by other meta-analysis investigations later. Such association of ABCA7 variants was reported on more specific findings of the disease such as memory decline and incident mild cognitive impairment or cortical and hippocampal atrophy. Protein-disrupting variants in ABCA7 have been shown to predispose to Alzheimer's disease. The Icelandic database of Decode Genetics has shown a doubled probability of developing Alzheimer's disease when inactive variants of the ABCA7 gene are present. By using the knock-out mice, ABCA7 was indicated involved in generation and processing of amyloid β (Aβ) peptides. In the brain of the amyloid precursor protein transgenic mice, deletion of ABCA7 resulted in accumulation of Aβ40 and Aβ42 in the early stage apparently by accelerating Aβ production. More rapid endocytosis of amyloid precursor protein was observed in primary microglia from ABCA7 deficient mice. Roles of ABCA7 are also implicated for microglial phagocytotic function and immune responses. Although the direct target of ABCA7 function is unclear, the findings are so far mechanistically consistent with the increased Aβ production. The data can be summarized as 1) loss of function of ABCA7 is associated with a risk for late onset Alzheimer's disease, 2) one of its molecular backgrounds can be enhanced production/decreased processing of Aβ peptides, and 3) ABCA7 is at least shown to increase phagocytosis including that of microglia. Since ABCA7 gene is down-regulated by cell cholesterol via the SRE/SREBP system, the data accumulated are consistent with clinical implication that use of statins, HMG-CoA reductase inhibitors, reduces risk for Alzheimer's disease. See also ATP-binding cassette transporter Notes References Further reading External links ATP-binding cassette transporters