Abstract
Anxiety is most common among Alzheimer's disease (AD) patients with an age at onset under age 65. Apolipoprotein E4 (apoE4) is a risk factor for developing AD at an earlier age and might contribute to this effect. In mice, apoE plays a role in the regulation of anxiety, which might involve histamine receptor-mediated signaling and steroidogenesis in the adrenal gland. In addition, human apoE isoforms have differential effects on anxiety in adult mice lacking apoE and probable AD patients. Compared to wild-type mice, mice lacking apoE and apoE4 mice showed pathological alterations in the central nucleus of the amygdala, which is involved in regulation of anxiety. ApoE4, but not mice lacking apoE, or apoE3 mice showed impaired dexamethasone suppression of plasma corticosterone. Understanding how apoE modulates measures of anxiety might help the developments of therapeutic targets to reduce or even prevent measures of anxiety in health and in dementing illnesses.
Highlights
Noncognitive behavioral changes are the major cause of institutionalization of Alzheimer’s disease (AD) patients and a major concern for their caregivers [1,2,3]
In AD, anxiety is inversely related to mini-mental state examination (MMSE) score [7]
A study describing the relationship between anxiety and nighttime behavioral disturbance in a community dwelling sample of 153 AD patients revealed symptoms of anxiety and patient awakening associated with higher levels of patient anxiety and patient impairments in activities of daily living (ADL) in 56% of the patients [10]
Summary
Noncognitive behavioral changes are the major cause of institutionalization of AD patients and a major concern for their caregivers [1,2,3] Such changes are a negative predictor of survival and quality of life for AD patients and contribute to increased costs [4, 5]. When measures of anxiety in the elevated plus maze were assessed in 6-month-old Apoe−/− male and wild-type control mice, Apoe−/− mice showed increased measures of anxiety [13]. These changes are age-dependent and not seen in 3-month-old mice
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