File this paper from Sultana and Butterfield under “early biological indicators of Alzheimer’s Disease (AD)” along with recent reports of MRI tests for mild cognitive impairment and potential microarray-based blood test for AD:
Mild cognitive impairment (MCI) is regarded as a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer’s disease (AD). Previous studies had demonstrated increased expression of cell cycle proteins in AD brain. In the present study, we have analyzed the expression of the cell cycle proteins, CDK2, CDK5 and cyclin G1 in hippocampus and inferior parietal lobule (IPL) in subjects with amnestic mild cognitive impairment and control using Western blot analysis. The expression of CDK2, CDK5 and cyclin G1 were found to be significantly increased in MCI hippocampus as well as in IPL compared to control brain. These results suggest that some cells may have re-entered the cell cycle. However, the expression of CDK2 and CDK5 is greater in MCI hippocampus compared to those of MCI IPL, and hippocampus is a region that is severely affected by AD pathology. Since these proteins are involved directly or indirectly in microtubule destabilization and hyperphosphorylation of tau, and also in APP processing we hypothesize that cell cycle disturbance may be important contributor in the pathogenesis of AD.
Unlike the MRI and blood-test assays, this finding is likely of little use as a diagnostic or prognostic tool — there’s not a safe noninvasive way to measure gene expression inside the brain of a living person, and I can’t imagine a biopsy-based assay becoming a standard part of the toolkit — but it’s nonetheless an importrant contribution to a growing literature about the neurological changes that precurse and predict Alzheimer’s later in life.
The expression of cyclin-dependent kinase (CDK) genes in the most affected (or to-be-affected) parts of the brain suggests to me that the stem cell compartment is waking up in response to early cell loss. We’ve discussed these stem cells in earlier entries, starting with my pleasant surprise at their existence (Neural progenitors in the adult human brain) and going on to describe the role of p16INK4a in the regulation of proliferation in this niche (p16 and neural progenitors in the brain).