RGD Reference Report - beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. - Rat Genome Database

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beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease.

Authors: Masliah, E  Rockenstein, E  Veinbergs, I  Sagara, Y  Mallory, M  Hashimoto, M  Mucke, L 
Citation: Masliah E, etal., Proc Natl Acad Sci U S A 2001 Oct 9;98(21):12245-50. Epub 2001 Sep 25.
RGD ID: 1302528
Pubmed: PMID:11572944   (View Abstract at PubMed)
PMCID: PMC59799   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.211412398   (Journal Full-text)

Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenetic pathways. We generated transgenic (tg) mice with neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The functional and morphological alterations in doubly tg mice resembled the Lewy-body variant of Alzheimer's disease. These mice had severe deficits in learning and memory, developed motor deficits before alpha-synuclein singly tg mice, and showed prominent age-dependent degeneration of cholinergic neurons and presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these inclusions were fibrillar in doubly tg mice, whereas all inclusions were amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted aggregation of alpha-synuclein in a cell-free system and intraneuronal accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may contribute to the development of Lewy-body diseases by promoting the aggregation of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal pathologies. Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IMP 1302528human gene in a mouse modelRGD 
Alzheimer's disease  ISOSNCA (Homo sapiens)1302528; 1302528human gene in a mouse modelRGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease pathway   ISS 1302528 RGD 
Alzheimer's disease pathway   ISOrno:050101302528 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Snca  (synuclein alpha)

Genes (Mus musculus)
Snca  (synuclein, alpha)

Genes (Homo sapiens)
SNCA  (synuclein alpha)


Additional Information