ApoE 4 Genotype Is Accompanied by Lower Metabolic Activity in Nucleus Basalis of Meynert Neurons in Alzheimer Patients and Controls as Indicated by the Size of the Golgi Apparatus

ABSTRACTWe previously found apolipoprotein (apoE) 4-dependent lower metabolic activity in nucleus basalis of Meynert (NBM) neurons in Alzheimer disease (AD). In the present study we examined the metabolic activity in the NBM of 39 mentally intact control subjects with different APOE genotype. The control subjects had either no AD pathology (Braak stage 0) or the very beginning of AD pathology (Braak stage I-II). We used the Golgi apparatus (GA) size as a measure of neuronal metabolic activity. Control subjects carrying an apoE 4 allele showed reduced neuronal metabolism; they had significantly more neurons with smaller GA sizes compared to control subjects not carrying an apoE 4 allele. Only control subjects not carrying an apoE 4 allele had increased neuronal metabolism in Braak I-II subjects. They had more neurons with larger GA sizes compared to Braak 0 subjects, which may reflect a compensatory mechanism. Our data indicate that APOE 4 may act by a lower neuronal metabolism as a risk factor for cognitive impairment in normal aging and early prodromal AD. As the disease progresses into later stages of AD (Braak V–VI) neuronal metabolism strongly diminishes, resulting in neurons with extremely small GA sizes, irrespective of APOE genotype.