Materials and Methods
Materials
Human Brain Specimens
Case number | Sex | Age, year | PMI, hour | 2012 NIA-Alz Assoc criteria | Diagnosis | MMSE score (months before death) |
---|---|---|---|---|---|---|
Control cases without AD-related pathology | ||||||
U1 | F | 40 | 4 | A0, B0, C0 | SCA | NA |
824 | F | 86 | 12.5 | A0, B0, C0 | N | 30 (5) |
789 | F | ≥90 | 9 | A0, B0, C0 | N | 30 (29) |
726 | F | ≥90 | 8.5 | A0, B0, C0 | N | NA |
810 | M | 81 | 5 | A0, B0, C0 | SCA | 27 (>120) |
779 | F | 89 | 12 | A0, B0, C0 | N | 29 (1) |
HPC cases | ||||||
2-11 | M | ≥90 | 4.1 | A1, B1, C1 | N | 28 (4) |
13-11 | F | ≥90 | 10.3 | A1, B1, C2 | CIND | 21 (3) |
4-12 | F | ≥90 | 5.25 | A2, B1, C2 | N | 28 (3) |
8-12 | M | ≥90 | 4 | A1, B1, C0 | N | 29 (5) |
11-12 | M | 86 | 5.25 | A1, B1, C0 | N | 27 (14) |
24-11 | M | 86 | 3.5 | A1, B2, C1 | CIND | 22 (18) |
27-10 | F | ≥90 | 4.3 | A0, B2, C0 | CIND | 29 (6) |
15-09 | M | 82 | 14.9 | A0, B2, C0 | Hippocampal sclerosis | 24 (58) |
33-10 | M | ≥90 | 6.05 | A3, B2, C2 | N | 29 (5) |
735 | M | 82 | 8.8 | A2, B2, C2 | N | NA |
34-11 | F | ≥90 | 4.25 | A1, B2, C1 | N | 30 (32) |
808 | M | ≥90 | 6 | A1, B3, C1 | N | 28 (22) |
22-12 | M | ≥90 | 6.5 | A2, B0, C1 | N | 25 (5) |
36-10 | M | ≥90 | 6 | A3, B2, C2 | CIND | 28 (4) |
38-10 | M | ≥90 | 9.4 | A2, B2, C2 | CIND | 24 (5) |
7-11 | F | ≥90 | 4.25 | A3, B2, C2 | CIND | 28 (5) |
Early-stage AD cases (Braak stage IV or less) | ||||||
830 | F | 89 | 4.25 | A1, B1, C2 | AD | NA |
787 | F | 87 | 9 | A2, B2, C2 | AD/mild CAA | NA |
3-12 | M | 81 | 5 | A2, B2, C2 | AD | 19 (33) |
34-10 | F | ≥90 | 4.45 | A2, B2, C1 | AD | 23 (41) |
9-11 | F | ≥90 | 6.35 | A3, B2, C3 | AD | 17 (4) |
835 | F | 78 | 6.5 | A1, B2, C1 | AD/Parkinson's disease | 23 (12) |
737 | F | 76 | 10.8 | A2, B2, C1 | AD | NA |
788 | M | 82 | 9.5 | A1, B2, C1 | AD/mild CAA | 23 (13) |
825 | F | 68 | 9.75 | A1, B2, C2 | AD | 15 (9) |
U2 | M | 75 | 13 | A1, B1, C2 | AD/Parkinson's disease | NA |
Late-stage AD cases (Braak stage V to VI) | ||||||
U3 | F | ≥90 | 6 | A2, B3, C2 | AD/Parkinson disease | NA |
811 | M | 59 | 5.5 | A3, B3, C3 | AD | NA |
11-09 | M | 77 | 5.5 | A3, B3, C3 | AD | NA |
U4 | F | 80 | 11 | A3, B3, C3 | AD | NA |
U5 | M | 82 | 5 | A3, B3, C3 | AD/Lewy body disease | NA |
10-09 | F | 82 | 4.5 | A3, B3, C3 | AD | 14 (>120) |
05-157 | F | 87 | 6 | A3, B3, C3 | AD | NA |
23-10 | M | 85 | 3.55 | A3, B3, C3 | AD | 5 (20) |
10-10 | F | 63 | 3.4 | A3, B3, C3 | AD | 2 (9) |
864 | M | 86 | 12 | A3, B3, C3 | AD | 2 (27) |
33-09 | M | ≥90 | 6.36 | A3, B3, C3 | AD | 19 (13) |
16-11 | F | 75 | 6.15 | A3, B3, C3 | AD | 13 (14) |
37-11 | F | ≥90 | 8 | A3, B3, C3 | AD/hippocampal sclerosis | 0 (12) |
819 | F | 80 | 5 | A2, B3, C2 | AD | NA |
Animals
- Teng E.
- Kepe V.
- Frautschy S.A.
- Liu J.
- Satyamurthy N.
- Yang F.
- Chen P.P.
- Cole G.B.
- Jones M.R.
- Huang S.C.
- Flood D.G.
- Trusko S.P.
- Small G.W.
- Cole G.M.
- Barrio J.R.
Flow Cytometric Analysis of Synaptosome-Enriched P-2 Fraction
Confocal Microscopy
Oligomeric and Total Aβ ELISA
Statistical Analysis
Results
Total in Situ Synaptic Aβ Is Associated with Plaque Level in Parietal Cortex
Synapse-Associated Soluble Oligomers Are Associated with Onset of Dementia
Progression of Total in Situ Synaptic Aβ and oAβ in a Transgenic Rat Model of AD
Synaptic p-Tau Is Not Elevated until Late-Stage AD in Parietal Cortex
Synaptic p-Tau Follows Amyloid Pathology in Aged Transgenic APP/PS1 Rats in the Absence of Tau Mutation or Overexpression
- Pooler A.M.
- Polydoro M.
- Wegmann S.K.
- Pitstick R.
- Kay K.R.
- Sanchez L.
- Carlson G.A.
- Gomez-Isla T.
- Albers M.W.
- Spires-Jones T.L.
- Hyman B.T.
- Sturchler-Pierrat C.
- Abramowski D.
- Duke M.
- Wiederhold K.H.
- Mistl C.
- Rothacher S.
- Ledermann B.
- Burki K.
- Frey P.
- Paganetti P.A.
- Waridel C.
- Calhoun M.E.
- Jucker M.
- Probst A.
- Staufenbiel M.
- Sommer B.
- Moechars D.
- Dewachter I.
- Lorent K.
- Reverse D.
- Baekelandt V.
- Naidu A.
- Tesseur I.
- Spittaels K.
- Haute C.V.
- Checler F.
- Godaux E.
- Cordell B.
- Van Leuven F.
P-Tau Immunolabeling Is Elevated in Individual Aβ-Positive Synaptosomes in Early AD
Discussion
- Aizenstein H.J.
- Nebes R.D.
- Saxton J.A.
- Price J.C.
- Mathis C.A.
- Tsopelas N.D.
- Ziolko S.K.
- James J.A.
- Snitz B.E.
- Houck P.R.
- Bi W.
- Cohen A.D.
- Lopresti B.J.
- DeKosky S.T.
- Halligan E.M.
- Klunk W.E.
- Rowe C.C.
- Ng S.
- Ackermann U.
- Gong S.J.
- Pike K.
- Savage G.
- Cowie T.F.
- Dickinson K.L.
- Maruff P.
- Darby D.
- Smith C.
- Woodward M.
- Merory J.
- Tochon-Danguy H.
- O'Keefe G.
- Klunk W.E.
- Mathis C.A.
- Price J.C.
- Masters C.L.
- Villemagne V.L.
- Yang D.S.
- Stavrides P.
- Mohan P.S.
- Kaushik S.
- Kumar A.
- Ohno M.
- Schmidt S.D.
- Wesson D.
- Bandyopadhyay U.
- Jiang Y.
- Pawlik M.
- Peterhoff C.M.
- Yang A.J.
- Wilson D.A.
- St George-Hyslop P.
- Westaway D.
- Mathews P.M.
- Levy E.
- Cuervo A.M.
- Nixon R.A.
- Perez-Nievas B.G.
- Stein T.D.
- Tai H.C.
- Dols-Icardo O.
- Scotton T.C.
- Barroeta-Espar I.
- Fernandez-Carballo L.
- de Munain E.L.
- Perez J.
- Marquie M.
- Serrano-Pozo A.
- Frosch M.P.
- Lowe V.
- Parisi J.E.
- Petersen R.C.
- Ikonomovic M.D.
- Lopez O.L.
- Klunk W.
- Hyman B.T.
- Gomez-Isla T.
- Perez-Nievas B.G.
- Stein T.D.
- Tai H.C.
- Dols-Icardo O.
- Scotton T.C.
- Barroeta-Espar I.
- Fernandez-Carballo L.
- de Munain E.L.
- Perez J.
- Marquie M.
- Serrano-Pozo A.
- Frosch M.P.
- Lowe V.
- Parisi J.E.
- Petersen R.C.
- Ikonomovic M.D.
- Lopez O.L.
- Klunk W.
- Hyman B.T.
- Gomez-Isla T.
- Koffie R.M.
- Meyer-Luehmann M.
- Hashimoto T.
- Adams K.W.
- Mielke M.L.
- Garcia-Alloza M.
- Micheva K.D.
- Smith S.J.
- Kim M.L.
- Lee V.M.
- Hyman B.T.
- Spires-Jones T.L.
- Dujardin S.
- Lecolle K.
- Caillierez R.
- Begard S.
- Zommer N.
- Lachaud C.
- Carrier S.
- Dufour N.
- Auregan G.
- Winderickx J.
- Hantraye P.
- Deglon N.
- Colin M.
- Buee L.
Acknowledgments
Supplemental Data
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Article info
Publication history
Footnotes
Supported by NIH grants AG27465 (K.H.G.), NS038328 (D.B.T.), and AG041295 (D.B.T.); National Institute on Aging (NIA) grants AG18879 (C.A.M.) and AG34628 (jointly sponsored by the NIA, American Federation for Aging Research, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor; to E.T.); the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers (D.B.T.); University of California Los Angeles Clinical and Translational Science Institute (UCLA CTSI) grant UL1TR000124 (E.Y.H.); UCLA Older Americans Independence Center grant P30 AG028748 (E.Y.H.); and the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine (H.V.V.). Tissue was obtained from the AD Research Center Neuropathology Cores NIA grants P50 AG05142 (USC), P50 AG16970 (UCLA), and P50 AG16573 (UC Irvine). Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility, supported by NIH grants CA16042 and AI 28697 and by the JCCC, the UCLA AIDS Institute, the David Geffen School of Medicine, and the Chancellor's Office at UCLA. Diagnosis, characterization, and follow-up of >90 study subjects was supported by NIA grant R01AG21055.
Disclosures: None declared.
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