Impact of increased APP gene dose in Down syndrome and the Dp16 mouse model.
Alzheimer's disease
Dp16
neurodegeneration
sex differences
trisomy 21
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
21
06
2021
received:
26
03
2021
accepted:
29
07
2021
pubmed:
11
11
2021
medline:
9
6
2022
entrez:
10
11
2021
Statut:
ppublish
Résumé
People with Down syndrome (DS) are predisposed to Alzheimer's disease (AD). The amyloid hypothesis informs studies of AD. In AD-DS, but not sporadic AD, increased APP copy number is necessary, defining the APP gene dose hypothesis. Which amyloid precursor protein (APP) products contribute needs to be determined. Brain levels of full-length protein (fl-hAPP), C-terminal fragments (hCTFs), and amyloid beta (Aβ) peptides were measured in DS, AD-DS, non-demented controls (ND), and sporadic AD cases. The APP gene-dose hypothesis was evaluated in the Dp16 model. DS and AD-DS differed from ND and AD for all APP products. In AD-DS, Aβ42 and Aβ40 levels exceeded AD. APP products were increased in the Dp16 model; increased APP gene dose was necessary for loss of vulnerable neurons, tau pathology, and activation of astrocytes and microglia. Increases in APP products other than Aβ distinguished AD-DS from AD. Deciphering AD-DS pathogenesis necessitates deciphering which APP products contribute and how.
Identifiants
pubmed: 34757693
doi: 10.1002/alz.12463
pmc: PMC9085977
mid: NIHMS1731479
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1203-1234Subventions
Organisme : NIA NIH HHS
ID : R01 AG055523
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072980
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS072026
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061151
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066519
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG068054
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS066072
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG070154
Pays : United States
Informations de copyright
© 2021 the Alzheimer's Association.
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