Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a
complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted
that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic
risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin
are presumed to be risk factors or biomarkers for stress- and age-related disorders.
Objective: The interplay between the APOE genotype and plasma biomarkers was examined in patients
with AD presenting with or without depression to contribute to understanding the interdependence of
various molecular mechanisms in the pathophysiology of AD.
Method: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin
concentrations were measured in 85 patients with AD and 44 elderly controls.
Results: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies
of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in
patients with AD compared to those in controls, independent of the presence of comorbid depressive
symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in
patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence
of depression or the severity of dementia in AD.
Conclusion: Our findings indicate the existence of a little-known specific APOE-mediated mechanism
that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the
APOE ε4 allele.