Mild to Moderate Alzheimer Dementia with Insufficient Neuropathological Changes

被引：97

作者：

Serrano-Pozo, Alberto ^{[1
,2
,10
]}

Qian, Jing ^{[3
]}

Monsell, Sarah E. ^{[4
,5
]}

Blacker, Deborah ^{[1
,6
,7
]}

Gomez-Isla, Teresa ^{[1
,2
]}

Betensky, Rebecca A. ^{[1
,7
]}

Growdon, John H. ^{[1
,2
]}

Johnson, Keith A. ^{[1
,2
]}

Frosch, Matthew P. ^{[1
,8
]}

Sperling, Reisa A. ^{[1
,9
]}

Hyman, Bradley T. ^{[1
,2
]}

机构：

[1] Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA 02129 USA

[2] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[3] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA

[4] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA

[5] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[6] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[7] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[8] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA

[9] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA

[10] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA

来源：

ANNALS OF NEUROLOGY | 2014年 / 75卷 / 04期

关键词：

NATIONAL INSTITUTE; DISEASE; PET; AUTOPSY;

D O I：

10.1002/ana.24125

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Recently, approximate to 16% of participants in an anti-A passive immunotherapy trial for mild-to-moderate Alzheimer disease (AD) had a negative baseline amyloid positron emission tomography (PET) scan. Whether they have AD or are AD clinical phenocopies remains unknown. We examined the 2005-2013 National Alzheimer's Coordinating Center autopsy database and found that approximate to 14% of autopsied subjects clinically diagnosed with mild-to-moderate probable AD have no or sparse neuritic plaques, which would expectedly yield a negative amyloid PET scan. More than half of these A-negative subjects have low neurofibrillary tangle Braak stages. These findings support the implementation of a positive amyloid biomarker as an inclusion criterion in future anti-A drug trials. Ann Neurol 2014;75:597-601

引用

页码：597 / 601

页数：5

共 19 条

[1]

[Anonymous], 1997, Neurobiol Aging, V18, pS1

[2] Molecular imaging with Pittsburgh compound B confirmed at autopsy - A case report [J].

Bacskai, Brian J. ;

Frosch, Matthew P. ;

Freeman, Stefanie H. ;

Raymond, Scott B. ;

Augustinack, Jean C. ;

Johnson, Keith A. ;

Irizarry, Michael C. ;

Klunk, William E. ;

Mathis, Chester A. ;

DeKosky, Steven T. ;

Greenberg, Steven M. ;

Hyman, Bradley T. ;

Growdon, John H. .

ARCHIVES OF NEUROLOGY, 2007, 64 (03) :431-434

[3] Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study [J].

Barthel, Henryk ;

Gertz, Hermann-Josef ;

Dresel, Stefan ;

Peters, Oliver ;

Bartenstein, Peter ;

Buerger, Katharina ;

Hiemeyer, Florian ;

Wittemer-Rump, Sabine M. ;

Seibyl, John ;

Reininger, Cornelia ;

Sabri, Osama .

LANCET NEUROLOGY, 2011, 10 (05) :424-435

[4] Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010 [J].

Beach, Thomas G. ;

Monsell, Sarah E. ;

Phillips, Leslie E. ;

Kukull, Walter .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2012, 71 (04) :266-273

[5] The National Alzheimer's Coordinating Center (NACC) database: The uniform data set [J].

Beekly, Duane L. ;

Ramos, Erin M. ;

Lee, William W. ;

Deitrich, Woodrow D. ;

Jacka, Mary E. ;

Wu, Joylee ;

Hubbard, Janene L. ;

Koepsell, Thomas D. ;

Morris, John C. ;

Kukull, Walter A. .

ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2007, 21 (03) :249-258

[6] NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].

BRAAK, H ;

BRAAK, E .

ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259

[7]

Clark CM, 2012, LANCET NEUROL, V11, P669, DOI 10.1016/S1474-4422(12)70142-4

[8] National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease [J].

Hyman, Bradley T. ;

Phelps, Creighton H. ;

Beach, Thomas G. ;

Bigio, Eileen H. ;

Cairns, Nigel J. ;

Carrillo, Maria C. ;

Dickson, Dennis W. ;

Duyckaerts, Charles ;

Frosch, Matthew P. ;

Masliah, Eliezer ;

Mirra, Suzanne S. ;

Nelson, Peter T. ;

Schneider, Julie A. ;

Thal, Dietmar Rudolf ;

Thies, Bill ;

Trojanowski, John Q. ;

Vinters, Harry V. ;

Montine, Thomas J. .

ALZHEIMERS & DEMENTIA, 2012, 8 (01) :1-13

[9] Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease [J].

Ikonomovic, Milos D. ;

Klunk, William E. ;

Abrahamson, Eric E. ;

Mathis, Chester A. ;

Price, Julie C. ;

Tsopelas, Nicholas D. ;

Lopresti, Brian J. ;

Ziolko, Scott ;

Bi, Wenzhu ;

Paljug, William R. ;

Debnath, Manik L. ;

Hope, Caroline E. ;

Isanski, Barbara A. ;

Hamilton, Ronald L. ;

DeKosky, Steven T. .

BRAIN, 2008, 131 :1630-1645

[10] Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study [J].

Ikonomovic, Milos D. ;

Abrahamson, Eric E. ;

Price, Julie C. ;

Hamilton, Ronald L. ;

Mathis, Chester A. ;

Paljug, William R. ;

Debnath, Manik L. ;

Cohen, Anne D. ;

Mizukami, Katsuyoshi ;

DeKosky, Steven T. ;

Lopez, Oscar L. ;

Klunk, William E. .

ACTA NEUROPATHOLOGICA, 2012, 123 (03) :433-447

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