FIGURE 8:

Proposed theoretical mechanistic pathway of aneuploidy and apoptosis in FTLD-MAPT and other tauopathies. On the basis of the evidence presented here, which shows that mutant MAPT-induced aneuploidy and apoptosis require cell division, we hypothesize that the expression of mutant forms of MAPT in the cells of FTLD-MAPT patients (or in patients with other tauopathies) would induce mitotic spindle defects, which would in turn lead to the accumulation of aneuploid cells over time as a result of aberrant cell division. An increase in the aneuploid cell population would not only place a heavy burden on the aneuploid cells to overcome the detrimental effects of altered gene dosage but also render them more vulnerable and prone to undergoing apoptosis.