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The relationship between amyloid and tau.

¹Laboratory of Neurogenetics, NIA/NIH, Building 10, 6C103, Bethesda, MD 20892, USA. hardyj@mail.nih.gov

Journal of Molecular Neuroscience : MN

|June 10, 2003

Summary

Genetic findings suggest amyloid precursor protein (APP)/amyloid-beta (Abeta) pathology precedes tau pathology in Alzheimer's disease. This relationship is complex, with APP/Abeta also linked to synuclein/Lewy bodies and tau pathology potentially triggered by other genetic factors.

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Area of Science:

Neuroscience
Genetics
Pathology

Background:

Alzheimer's disease pathogenesis involves amyloid precursor protein (APP)/amyloid-beta (Abeta) and tau pathologies.
The precise relationship and order of these pathologies remain under investigation.

Purpose of the Study:

To discuss the relationship between APP/Abeta and tau/tangle pathologies based on genetic findings.
To propose a model where APP/Abeta is upstream of tau/tangle in Alzheimer's pathogenesis.

Main Methods:

Analysis of genetic findings related to Alzheimer's disease pathologies.
Discussion of the interconnectedness of APP/Abeta, tau/tangle, and synuclein/Lewy body pathologies.

Main Results:

Genetic evidence supports APP/Abeta pathology being upstream of tau/tangle pathology in Alzheimer's disease.
The interplay between these pathologies is promiscuous: APP/Abeta can precede synuclein/Lewy bodies, and tau pathology can be initiated by other genetic factors.

Conclusions:

APP/Abeta acts as an upstream factor in Alzheimer's pathogenesis.
The initiation and progression of Alzheimer's pathologies are multifactorial and interconnected.

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