Alzheimer's Amyloidopathy: An Alternative Aspect
Björn Regland1, Andrew McCaddon2
1Institute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden.
Journal of Alzheimer'S Disease : JAD
|March 1, 2019
Summary
Alzheimer's disease (AD) research may have a common pathway. Genetic mutations and sporadic AD share links to reduced protease activity and vitamin B12 deficiency, suggesting new therapeutic targets for Alzheimer's disease.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- The amyloid hypothesis for Alzheimer's disease (AD) has not yielded effective treatments.
- Genetic mutations in amyloid precursor protein (APP) and presenilin-1 (PSEN1) are linked to AD pathogenesis.
- High-dose B-vitamins show promise in slowing brain atrophy in pre-AD states.
Purpose of the Study:
- To propose a unifying hypothesis linking sporadic and genetic forms of Alzheimer's disease.
- To investigate the role of homocysteine, B-vitamin deficiencies, and protease activity in AD.
- To explore the connection between APP/PSEN1 mutations and reduced vitamin B12 bioavailability.
Main Methods:
- Correlational analysis of serum homocysteine, B-vitamin levels, and protease inhibitors in AD patients and families.
- Review of existing literature on APP and PSEN1 mutations and their impact on cellular functions.
- Comparison of biochemical markers and genetic factors across different AD etiologies.
Main Results:
- Increased serum homocysteine, a marker for B-vitamin deficiency, is a risk factor for sporadic AD and correlates with protease inhibitors.
- Individuals with APP mutations and dementia exhibit low vitamin B12 levels, potentially linked to APP's protease inhibitor domain.
- PSEN1 mutations impair lysosomal function and trap vitamin B12, causing intracellular deficiency.
Conclusions:
- APP and PSEN1 mutations may reduce protease activity and vitamin B12 availability.
- Sporadic AD presents with increased protease inhibition and B-vitamin deficiencies, particularly B12.
- These findings suggest a common neuropathogenic pathway in diverse AD etiologies, warranting further investigation.
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