Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease.
BACKGROUND
Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used.


METHODS
Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change.


RESULTS
Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted κ = .88, 95% confidence interval: 0.77-0.95) and good-to-excellent agreement for the three supporting scores. Some improvement was observed with consensus evaluation but not with central staining of slides. Evaluation of glass slides and digitally prepared whole-slide images was comparable.


CONCLUSIONS
AD neuropathologic evaluation as performed across AD Centers yields data that have high agreement with potential modifications for modest improvements.
Department of Pathology, University of Washington, Seattle, WA, USA. Electronic address: tmontine@u.washington.edu.
Thomas J
TJ
Montine
National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA.
Sarah E
SE
Monsell
Banner Sun Health Research Institute, Civin Laboratory for Neuropathology, Sun City, AZ, USA.
Thomas G
TG
Beach
Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Eileen H
EH
Bigio
National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA.
Yunqi
Y
Bu
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Nigel J
NJ
Cairns
Department of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charleston, MA, USA.
Matthew
M
Frosch
Department of Pathology, University of Washington, Seattle, WA, USA.
Jonathan
J
Henriksen
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Julia
J
Kofler
National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA.
Walter A
WA
Kukull
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Edward B
EB
Lee
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Pathology Department, University of Kentucky, Lexington, KY, USA.
Peter T
PT
Nelson
Department of Pathology, University of Washington, Seattle, WA, USA.
Aimee M
AM
Schantz
Department of Pathology Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Julie A
JA
Schneider
Department of Pathology, University of Washington, Seattle, WA, USA.
Joshua A
JA
Sonnen
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
John Q
JQ
Trojanowski
Department of Pathology & Laboratory Medicine (Neuropathology) David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
Harry V
HV
Vinters
National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA.
Xiao-Hua
XH
Zhou
Department of Neurology, Massachusetts General Hospital, Charleston, MA, USA; Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Charleston, MA, USA.
Bradley T
BT
Hyman
D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D006801:Humans; D054561:National Institute on Aging (U.S.); D000069338:Neuropathology / Q000379:methods / Q000592:standards*; D017410:Practice Guidelines as Topic; D014481:United States; D014837:Voluntary Health Agencies
Alzheimer's disease; Methods; Multisite; Neuropathology; Whole-slide imaging