@article{d2e4eedfafb34fd0883aa61cdacbb84d,
title = "Knowledge gaps in Alzheimer's disease immune biomarker research",
abstract = "Considerable evidence has accumulated implicating a role for immune mechanisms in moderating the pathology in Alzheimer's disease dementia. However, the appropriate therapeutic target, the appropriate direction of manipulation, and the stage of disease at which to begin treatment remain unanswered questions. Part of the challenge derives from the absence of any selective pressure to develop a coordinated beneficial immune response to severe neural injury in adults. Thus, immune responses to the prevailing stimuli are likely to contain both beneficial and detrimental components. Knowledge gaps include: (1) how a biomarker change relates to the underlying biology, (2) the degree to which pathological stage group differences reflect a response to pathology versus trait differences among individuals regulating risk of developing pathology, (3) the degree to which biomarker levels are predictive of subsequent changes in pathology and/or cognition, and (4) experimental manipulations in model systems to determine whether differences in immune biomarkers are causally related to pathology.",
author = "Morgan, {David G.} and Mielke, {Michelle M.}",
note = "Funding Information: We thank Richard Ransohoff for multiple informative discussions and for sharing the concept that natural selection had no influence on the immune reaction to neurodegeneration. We thank Elana Perry for assisting with the search for blood-based biomarkers and reviewing the manuscript for clarity to readers outside the biomarker field. We further thank Brianne Bettcher for reading and commenting upon the manuscript and coordinating the series of reviews from the Immunity and Neurodegeneration PIA from ISTAART. DGM was supported by grants from the National Institutes of Health (R01 AG 051500, R56 AG058234, R44 AG058330, R01 AG062217, and R01 AG051674) and funds from the Spectrum-MSU Alliance. MMM was supported by grants from the National Institutes of Health (U01 AG06786, R01 AG049704, P30 AG062677). Funding Information: We thank Richard Ransohoff for multiple informative discussions and for sharing the concept that natural selection had no influence on the immune reaction to neurodegeneration. We thank Elana Perry for assisting with the search for blood‐based biomarkers and reviewing the manuscript for clarity to readers outside the biomarker field. We further thank Brianne Bettcher for reading and commenting upon the manuscript and coordinating the series of reviews from the Immunity and Neurodegeneration PIA from ISTAART. DGM was supported by grants from the National Institutes of Health (R01 AG 051500, R56 AG058234, R44 AG058330, R01 AG062217, and R01 AG051674) and funds from the Spectrum‐MSU Alliance. MMM was supported by grants from the National Institutes of Health (U01 AG06786, R01 AG049704, P30 AG062677). Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association",
year = "2021",
month = dec,
doi = "10.1002/alz.12342",
language = "English (US)",
volume = "17",
pages = "2030--2042",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "12",
}