Alzheimer’s disease and its symptoms in patients are well described on the web pages of the Alzheimer’s Society.
In summary AD:
- Is the most prevalent form of (age-related) dementia
- Cannot be cured
- Is currently only transient and moderately improved by symptomatic treatment
- Has epidemic-like proportions with close to 26 millions patients diagnosed worldwide
(projections: more than 100 millions in 2050)
- Is a major challenge for society and public health systems, as late stage patients need 24/7 monitoring
The molecular causes of the disease are still not fully understood. However, the amyloid precursor protein (APP) on chromosome 21 is involved in AD, because:
- Trisomy 21 patients always get AD like symptoms early in life
- Rare (<1% of AD patients) APP mutations result in early onset AD
- Oligomers of Aβ peptides are neurotoxic, inducing cognitive defects
The amyloid hypothesis has been around for more than 20 years, predicting that Aβ peptides and their macromolecular aggregates called “plaques” cause the disease. However, Aβ peptide monomers are not toxic, but likely beneficial for brain function. Plaque aggregates are neither toxic nor well correlated with dementia as shown e.g. in the continuing longitudinal Nun study where strong AD plaque pathology in non-demented people was explained by “brain reserves” (www.healthstudies.umn.edu/nunstudy/articles).
Recently it was found that low molecular weight soluble oligomers of Aβ are formed in AD brains and that these oligomers are highly toxic to important brain targets involved in cognition. Furthermore, Aβ oligomers are thought to induce holes in the cell membrane (www.mdpi.com/1422-0067/13/6/7303/pdf). A review on Aβ oligomer toxicity can be found here: http://www.nature.com/neuro/journal/v15/n3/full/nn.3028.html.
SynAging scientists have contributed significantly to the field of Aβ oligomer toxicity (http://www.neurobiologyofaging.org/article/S0197-4580(07)00115-7/abstract) and established very reliable, fast and cost-effective models. These models are based on proprietary Aβ peptide oligomer preparations of various Aβ peptides (link to table). These models have been established in 2010 and since then are used on a continuous base by many international clients.