Down-regulation of trkA mRNA within nucleus basalis neurons in individuals with mild cognitive impairment and Alzheimer's disease.

ABSTRACT

Recent studies indicate that trkA expression is reduced in end-stage Alzheimer's disease (AD). However, understanding the neuropathologic correlates of early cognitive decline, as well as the changes that underlie the transition from nondemented mild cognitive impairment (MCI) to AD, are more critical neurobiological challenges. In these regards, the present study examined the expression of trkA mRNA in individuals diagnosed with MCI and AD from a cohort of people enrolled in a Religious Orders Study. Individuals with MCI and AD displayed significant reductions in trkA mRNA relative to aged-matched controls, indicating that alterations in trkA gene expression occur early in the disease process. The magnitude of change was similar in MCI and AD cases, suggesting that further loss of trkA mRNA is not necessarily associated with the transition of individuals from nondemented MCI to AD. The loss of trkA mRNA was not associated with education, apolipoprotein E allele status, gender, Braak score, global cognitive score or Mini-Mental Status Examination. In contrast, the loss of trkA mRNA in MCI and AD was significantly correlated with function on a variety of episodic memory tests.