From the Guidelines
Protein loss in Alzheimer's disease is a critical aspect of the disease's progression, with key proteins such as amyloid-beta, tau, synaptophysin, and PSD-95 becoming dysfunctional or depleted, leading to neurodegeneration and cognitive decline. The loss of these proteins occurs through multiple mechanisms, including abnormal protein folding, impaired clearance systems, oxidative stress damage, and neuroinflammation, as noted in studies on the molecular mechanisms of Alzheimer's disease 1.
Key Proteins Affected
- Amyloid-beta: forms plaques outside neurons
- Tau protein: creates neurofibrillary tangles inside neurons when hyperphosphorylated
- Synaptic proteins (synaptophysin and PSD-95): essential for communication between neurons
- Neurotrophic factors (BDNF and NGF): decrease, reducing support for neuronal survival
Mechanisms of Protein Dysregulation
- Abnormal protein folding
- Impaired clearance systems (ubiquitin-proteasome system and autophagy)
- Oxidative stress damage
- Neuroinflammation
Nutritional Considerations
Studies suggest that nutritional interventions may play a role in reducing the risk of Alzheimer's disease, with certain dietary components potentially influencing protein aggregation and clearance, such as curcumin, oleocanthal, and cinnamon extract 1. However, the evidence on protein intake and Alzheimer's disease is complex, with high protein intake potentially being detrimental in the non-elderly, while low protein intake in the elderly may lead to reduced muscle mass and decreased IGF-1 levels 1.
Clinical Implications
Given the complexity of protein loss in Alzheimer's disease, a personalized approach to nutrition and care is essential, taking into account the individual's overall health, dietary needs, and disease stage. Caregivers play a critical role in managing nutritional problems in individuals with Alzheimer's disease, and their own nutritional status and well-being should also be considered, as noted in guidelines on nutrition in dementia 1.
From the Research
Protein Loss in Alzheimer's Disease
- Alzheimer's disease (AD) is characterized by the deposition of senile plaques and the formation of neurofibrillary tangles, as well as neuronal dysfunctions in the brain 2.
- The protein quality control system, which includes the endoplasmic reticulum system, autophagy-lysosome system, and the ubiquitin-proteasome system, plays a crucial role in recognizing and modulating the turnover of damaged proteins 2.
- The accumulation of abnormal proteins in AD is closely related to the dysfunction of the protein quality control system, and changes in the synthesis, degradation, and removal of essential biological components occur in the early stage of AD 2.
Relationship Between Protein Quality Control and Alzheimer's Disease
- The protein quality control system is essential for maintaining protein homeostasis, and its dysfunction can lead to the accumulation of toxic protein aggregates 3.
- Soluble intermediates of aggregation, or oligomers, may be the key species that mediate toxicity and underlie seeding and spreading in AD 3.
- The structural features of toxic intermediates and the mechanisms by which oligomers cause cell toxicity are crucial for understanding the pathogenesis of AD 3.
Potential Therapeutic Approaches
- Supplementation with carotenoids, omega-3 fatty acids, and vitamin E may have a positive effect on the symptoms and progression of AD 4.
- Omega-3 fatty acids may act as a possible protection factor in AD, although the effects are most effectively demonstrated in patients with very mild AD 5.
- Further research is needed to fully understand the relationship between protein quality control and AD, and to explore potential therapeutic approaches 2, 6.