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

Recent studies indicate that trkA expression is reduced in end-stage Alzhei mer's disease (AD). However, understanding the neuropathologic correlates o f early cognitive decline, as well as the changes that underlie the transit ion from nondemented mild cognitive impairment (MCI) to AD, are more critic al 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 M CI and AD displayed significant reductions in trkA mRNA relative to aged-ma tched controls, indicating that alterations in trkA gene expression occur e arly 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 ass ociated with the transition of individuals from nondemented MCI to AD. The loss of trkA mRNA was not associated with education, apolipoprotein E allel e status, gender, Braak score, global cognitive score or Mini-Mental Status Examination. In contrast, the loss of trkA mRNA in MCI and AD was signific antly correlated with function on a variety of episodic memory tests. J. Co mp. Neurol. 437:296-307, 2001. (C) 2001 Wiley-Liss, Inc.