Alzheimer's Disease: Mechanism and Approach to Cell Therapy

Abstract

Alzheimer's disease (AD) is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late-onset AD pathogenesis being underpinned by different mechanisms. Most animal models of AD are generated from gene mutations involved in early onset familial AD, accounting for only 1% of all cases, which may consequently complicate our understanding of AD mechanisms. In this article, the authors discuss the pathogenesis of AD according to the two main neuropathologies, including senescence-related mechanisms and possible treatments using stem cells, namely mesenchymal and neural stem cells.

Keywords: Alzheimer’s disease; Tau; amyloid-β; mesenchymal stem cells; neural stem cells.

Figure 1

The latency in seconds to find a hidden platform within 60 s over 10 consecutive days of testing is presented for each group: C57BL/6 (A); 129S2/SvHsd (B); and the triple transgenic mouse model of Alzheimer’s disease (AD) (3xTg-AD) (C). Latencies obtained from individual animals are plotted by different marks. Solid black lines show average latencies calculated for each day.

Figure 2

The total time (in seconds) spent in each quadrant (Q1, Q2, Q3, and Q4) during a 60-s probe trial (without the escape platform which was placed in Q3 during the 10-day training) is presented for the three strains of mice (A–C). Each individual animal’s time is plotted by different marks. Solid black lines show the mean time spent in each quadrant.