Apolipoprotein E and Alzheimer's disease: Therapeutic implications

Apolipoprotein E (APOE) is a plasma protein that plays an important role in cholesterol transport. The protein exists in 3 different isoforms coded for by alleles ε2, ε3 and ε4. Recent studies have shown that frequency of the APOE ε4 allele is much greater among individuals with Alzheimer's disease than age-matched healthy controls [an approximate 4-fold increase (36.6 vs 9.4%) in one recent study]. However, due to an insufficient sensitivity of the APOE ε4 allele in detecting patients with Alzheimer's disease and the presence of this allele in demented and nondemented individuals. APOE genotyping should not be used alone as a sole diagnostic test for Alzheimer's disease. An additional recent finding is that central muscarinic receptor binding, as revealed by positron emission tomography (PET) and [¹¹C]benztropine, declines with the progression of Alzheimer's disease regardless of the presence or absence of APOE ε4 allele. These findings suggest that measures of acetylcholine neurotransmission in the living Alzheimer's disease brain by PET help to visualise altered cholinergic function during the clinical course of Alzheimer's disease and to identify appropriate individuals who are more likely to respond to emerging cholinergic interventions.