Alzheimer's Disease

Alzheimer’s disease (AD) is categorized as a devastating neurodegenerative disease that irreversibly and progressively destroys memory, language abilities and thinking skills; inevitably leading to confusion and language breakdown [1]. “AD affects 35 million people worldwide and is the most common form of dementia among people aged 65 and older, progressing slowly from mild forgetfulness to the need for total care… Accumulating evidence supports the hypothesis that oxidative stress generated by various mechanisms maybe among the major intermediary risk factors that initiate and promote neurodegradation, leading to AD” [2]. Moreover, the observation of elevated concentrations of Iron as well as other metals and their imbalance in the central nervous system (CNS) modulate amyloid β (Aβ) formation and extracellular deposition, ultimately causing neurooxidative damage.

Soluble Aβ peptide is normally secreted by brain cells, and any excess is cleared. However, in abnormal conditions, Aβ self-aggregates, forming oligomers and amyloid fibrils. Oligomers exhibit neurotoxicity, and fibrils together with chaperone proteins form plaques that not only damage neurons but attract reactive astrocytes and microglia, resulting in further damage to the brain [3].

The common pathological feature associated with AD; cerebrovascular Amyloid β accumulation and formation of plaques in the cerebral vasculature; i.e. the arteries supplying oxygen and nutrients to the brain tissue, according to the amyloid hypothesis, is the key event leading to development of the pathology. Aβ peptides range from 39 to 42 amino acid residues and have a molecular weight of 4 kDa, with the most abundant being  Aβ40 peptide, which is responsible for generating between 80 and 90% of the total Aβ produced. In vitro studies have shown that the incubation of this peptide with cells in culture actually induces a significant neurotoxic effect exemplified by oxidative stress, apoptosis, and damage to membrane and cytoplasmic proteins, mitochondrial DNA and lipids. Also amyloid proteins can cause lipid peroxidation by inserting itself into the lipid bilayer; which causes a massive influx of Ca²⁺   and ultimately causing mitochondrial dysfunction, synapse loss, and, finally, neuronal death [4].

References

1. Devadhasan J, Kim S and An J (2011) Fish-on-a-chip: a sensitive detection microfluidic system for Alzheimer’s disease. Journal of Biomedical Science. 18(33).
2. Liu G, Men P, Perry G, and Smith M (2010) Nanoparticle and Iron Chelators as a Potential Novel Alzheimer Therapy. NIH Public Access. 610, 123-144.
3. Cheng K, Yeung C, Ho S, Chow S, Chow A and Baum L (2013) Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice. AAPS Journal. 15(2), 324-336.
4. Biomarkers of Alzheimer’s Disease in Vitro. ASC Chemical Neuroscience. 2,500-505.