Subcellular injuries in Alzheimer's disease.
Jean-Paul Tillement, Vassilios Papadopoulos1
1Research Institute of the McGill University Health Center, Montreal General Hospital, 1650 Cedar Avenue, C10-148, Montreal, Quebec H3G 1A4, Canada. vassilios.papadopoulos@mcgill.ca.
CNS & Neurological Disorders Drug Targets
|October 31, 2013
Summary
Alzheimer's disease begins with subcellular injuries at the Golgi apparatus, preceding amyloid buildup. This sequence leads to neuroinflammation and cell death, offering potential new drug targets.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Alzheimer's disease (AD) is a leading cause of dementia in older adults.
- Multiple hypotheses exist for AD pathophysiology, including amyloidogenesis and tau hyperphosphorylation.
- Understanding the sequence of subcellular events is crucial for identifying therapeutic targets.
Purpose of the Study:
- To review and sequence subcellular injuries in Alzheimer's disease (AD).
- To correlate cellular and subcellular events with neurodegeneration and cell death in AD.
- To identify the earliest subcellular defects initiating AD pathogenesis.
Main Methods:
- Review of experimental models, clinical symptoms, and autopsy reports of AD.
- Analysis of the temporal order of subcellular events in AD pathogenesis.
- Examination of the role of Golgi apparatus, lysosomes, and inflammatory processes.
Main Results:
- Subcellular injuries initiate at the Golgi apparatus before beta-amyloid deposition.
- Lysosomal dysfunction and impaired beta-amyloid clearance follow Golgi alterations.
- Neuroinflammation, originating in intracellular organelles, precedes widespread neurodegeneration and cell death.
Conclusions:
- The sequence of subcellular events in AD begins with Golgi apparatus injury.
- Lysosomal dysfunction and intracellular inflammation are key steps leading to neurodegeneration.
- Identifying the precise sequence of events may reveal novel therapeutic targets for Alzheimer's disease.
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