@article{aff30b8f9e394e9f8f4ff42cf1c34f75,
title = "Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease",
abstract = "Mechanisms underlying the protective effect of apolipoprotein E (APOE) ε2 against Alzheimer disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers. Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ɛ2/ɛ3 AD cases and controls. We also identified an APOE ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes and oligodendrocyte progenitor cells containing the genes C4A, C4B, and HSPA2. These genes were significantly associated with the ratio of phosphorylated tau at position 231 to total Tau but not with amyloid-β 42 level, suggesting this APOE ɛ2 related co-expression network may primarily be involved with tau pathology. HSPA2 expression was oligodendrocyte-specific and significantly associated with C4B protein. Our findings provide the first evidence of a crucial role of the complement pathway in the protective effect of APOE ε2 for AD.",
author = "Rebecca Panitch and Junming Hu and Jaeyoon Chung and Congcong Zhu and Gaoyuan Meng and Weiming Xia and Bennett, {David A.} and Lunetta, {Kathryn L.} and Tsuneya Ikezu and Rhoda Au and Stein, {Thor D.} and Farrer, {Lindsay A.} and Jun, {Gyungah R.}",
note = "Funding Information: This study was supported by the National Institute on Aging (NIA) grants RF1-AG057519, R01-AG048927, P30-AG013846, U01-AG032984, U19-AG068753, U01-AG062602, U01-AG058654, RF1-AG054156, RF1-AG08122, RF1-AG054076, RF1-AG054199, R01-AG066429, and R01-AG054672, and by Framingham Heart Study contracts 75N92019D00031 and HHSN2682015000011. Collection of study data provided by the Rush Alzheimer{\textquoteright}s Disease Center, Rush University Medical Center, Chicago was supported through funding by NIA grants P30-AG10161, R01-AG15819, R01-AG17917, R01-AG30146, R01-AG36836, U01-AG32984, U01-AG46152, and U01-AG61358, and funding from the Illinois Department of Public Health and the Translational Genomics Research Institute. Study data were also provided by Dr. Nil{\"u}fer Ertekin-Taner and Dr. Steven G. Younkin, Mayo Clinic, Jacksonville, FL using samples from the Mayo Clinic Study of Aging, the Mayo Clinic Alzheimer{\textquoteright}s Disease Research Center, and the Mayo Clinic Brain Bank. Collection of these data was supported through funding by NIH grants P50-AG016574, R01-AG032990, U01-AG046139, R01-AG018023, U01-AG006576, U01-AG006786, R01-AG025711, R01-AG017216, R01-AG003949, and R01-NS080820, and by funding from the CurePSP Foundation and the Mayo Foundation. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = oct,
doi = "10.1038/s41380-021-01266-z",
language = "English (US)",
volume = "26",
pages = "6054--6064",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "10",
}