Stem Cells from Adipose Tissue
Executive summary: Alzheimer’s Disease
Alzheimer’s disease (AD) is the leading cause of age related dementia, afflicting one in every eight people over the age of 65. Unfortunately, the incidence of dementia is expected to quadruple over the next 40 years, such that more than 115 million people will be afflicted world-wide by 2050. Currently approved therapies offer only marginal, temporary relief and fail to modify the underlying disease pathology. Thus, there is a critical and urgent need to examine novel and combinatorial approaches to treat this devastating disorder.
Pathologically, AD is characterized by the accumulation of three hallmark brain lesions, beta-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs) and inflammatory processes leading to death of neurons. Aβ plaques result from the extracellular accumulation of insoluble aggregates of a small 40 to 42 amino acid peptide, Aβ. NFTs in contrast, consist of intraneuronal insoluble aggregates of the microtubule binding protein, tau, which becomes hyper phosphorylated and compromises neuronal activity, connectivity and function.
In addition to the accumulation of Aβ and tau across multiple brain regions, AD patients also exhibit inflammation and widespread synaptic and neuronal loss. Given the complex nature of this disease and the multiple pathways and regions affected, a single small molecule approach may not provide substantial benefit in the absence of other interventions. Biologic-based approaches, such as stem cell transplantation, are therefore receiving increasing attention. Neural stem cell (NSC) transplantation markedly improves cognitive function, synaptic connectivity and neuronal survival in models of AD and tauopathy. Many of these effects appear to be mediated by stem cell derived neurotrophins or other neuroprotective activities. Mesenchymal stem cells have also been found to improve cognition in AD models by modulating complex biological Systems via multiple mechanisms.