Publications

Authors:

Piccini, A.; Zanusso, Gianluigi; Borghi, R.; Noviello, C.; Monaco, Salvatore; Russo, R.; Damonte, G.; Armirotti, A.; Gelati, Matteo; Giordano, R.; Zambenedetti, P.; Russo, C.; Ghetti, B.; Tabaton, M.

Title:

Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype

Year:

2007

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

Sì

Name of journal:

Archives of Neurology

ISSN of journal:

0003-9942

N° Volume:

64

Number or Folder:

5

Page numbers:

738-745

Keyword:

AMYLOID-BETA-PROTEIN, GAMMA-SECRETASE ACTIVITY, TRANSMEMBRANE ASPARTATES, TRANSGENIC MICE, DOWNS-SYNDROME, GENE, BRAIN, HETEROGENEITY, FAMILIES, PEPTIDE

Short description of contents:

OBJECTIVE: To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype. DESIGN: Description of a novel phenotype associated with a presenilin 1 mutation. SETTING: The subject was an outpatient who was diagnosed at the local referral center. PATIENT: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected. MAIN OUTCOME MEASURES: We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue. RESULTS: The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42. CONCLUSION: These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition.

Product ID:

38544

Handle IRIS:

11562/310560

Deposited On:

August 17, 2007

Last Modified:

November 15, 2022

Bibliographic citation:

Piccini, A.; Zanusso, Gianluigi; Borghi, R.; Noviello, C.; Monaco, Salvatore; Russo, R.; Damonte, G.; Armirotti, A.; Gelati, Matteo; Giordano, R.; Zambenedetti, P.; Russo, C.; Ghetti, B.; Tabaton, M., Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype «Archives of Neurology» , vol. 64 , n. 5 , 2007 , pp. 738-745

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