TY - JOUR
T1 - Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease
AU - Dominantly Inherited Alzheimer Network
AU - Schindler, Suzanne E.
AU - Li, Yan
AU - Todd, Kaitlin W.
AU - Herries, Elizabeth M.
AU - Henson, Rachel L.
AU - Gray, Julia D.
AU - Wang, Guoqiao
AU - Graham, Danielle L.
AU - Shaw, Leslie M.
AU - Trojanowski, John Q.
AU - Hassenstab, Jason J.
AU - Benzinger, Tammie L.S.
AU - Cruchaga, Carlos
AU - Jucker, Mathias
AU - Levin, Johannes
AU - Chhatwal, Jasmeer P.
AU - Noble, James M.
AU - Ringman, John M.
AU - Graff-Radford, Neill R.
AU - Holtzman, David M.
AU - Ladenson, Jack H.
AU - Morris, John C.
AU - Bateman, Randall J.
AU - Xiong, Chengjie
AU - Fagan, Anne M.
N1 - Publisher Copyright:
© 2019 the Alzheimer's Association
PY - 2019/5
Y1 - 2019/5
N2 - Introduction: Four less well-studied but promising “emerging” cerebrospinal fluid (CSF)biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Methods: CSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations. Results: The four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235)versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15–19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset. Discussion: Early abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation.
AB - Introduction: Four less well-studied but promising “emerging” cerebrospinal fluid (CSF)biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Methods: CSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations. Results: The four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235)versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15–19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset. Discussion: Early abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation.
KW - Alzheimer's disease
KW - Autosomal-dominant Alzheimer's disease
KW - Biomarkers
KW - Cerebrospinal fluid
KW - Dementia
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=85062285334&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.12.019
DO - 10.1016/j.jalz.2018.12.019
M3 - Article
C2 - 30846386
AN - SCOPUS:85062285334
SN - 1552-5260
VL - 15
SP - 655
EP - 665
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 5
ER -