59. APOE polymorphism and cortical plasticity are independently associated with cognitive decline in Alzheimer’s disease

Abstract

The potential effects of APOE isoforms on lipid metabolism, cell signaling, and neurotoxicity in the central nervous system have the potential to influence Alzheimer’s disease (AD). Several studies demonstrate that APOE E4 allele associates not only with AD risk and a lower age onset, but also with faster cognitive decline and greater cerebral atrophy, suggesting a key role of this polymorphism in modulating both disease risk and clinical outcome. In the current study, we investigated the correlation between cognitive decline, motor cortical plasticity and cerebrospinal fluid (CSF) biomarkers profile of AD patients divided by APOE polymorphism in E4 allele carriers (E4) and homozygous E3 carriers. A monophasic Magstim 200 device was used to deliver intermitted/continuous theta burst stimulation (iTBS/cTBS) protocols. ELISA was used for determination of CSF protein concentrations. Forty-one AD patients underwent lumbar puncture for CSF withdrawal, blood screening for APOE polymorphism, neurostimulation protocols applied over the primary motor cortex and repeated mini mental state examination (MMSE) at 6-, 12- and 18-months. No difference was found in CSF biomarkers profile within the APOE variants group. Conversely iTBS after effects were significantly reduced in E3 AD in comparison with E4 AD patients. MMSE progression, evaluated as delta between 18-month and baseline MMSE score (delta-MMSE) was higher, although not significantly, for E4 AD patients. Correlation analyses revealed that the individual amount of iTBS induced plasticity did correlate with delta-MMSE and total Tau (t-Tau), showing that a less pronounced LTP-like plasticity and higher t-Tau CSF levels were associated with a higher delta-MMSE. Finally a multivariate analysis showed that APOE polymorphism and LTP-like plasticity, but not t-Tau levels are independently able to predict delta-MMSE in AD patients. These findings demonstrate that cortical plasticity impairment in AD patients is significantly different according to APOE variants. Moreover APOE polymorphism and LTP-like plasticity are both independently associated with clinical progression in AD patients. APOE variants show different level of cortical plasticity and are independently associated with clinical progression in AD patients.