Analysis of data derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) program showed
plasma leptin levels in individuals with Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD) to be lower than
those of subjects with normal cognition (NC). Approximately 70% of both men and women with MCI have plasma leptin
levels lower than the median values of NC. Additionally, half of these subjects carry at least one apolipoprotein-E4
(APOE-ε4) allele. A subgroup of participants also had cerebrospinal fluid (CSF) leptin measured. Plasma leptin typically
reflected the levels of leptin in CSF in all groups (Control/MCI/AD) in both genders. The data suggest that plasma leptin
deficiency provides an indication of potential CNS leptin deficiency, further supporting the exploration of plasma leptin as
a diagnostic marker for MCI or AD. The important question is whether leptin deficiency plays a role in the causation of
AD and/or its progression. If this is the case, individuals with early AD or MCI with low plasma leptin may benefit from
leptin replacement therapy. Thus, these data indicate that trials of leptin in low leptin MCI/early-stage AD patients should
be conducted to test the hypothesis.
Keywords: Alzheimer's disease neuroimaging initiative, Alzheimer's disease, apolipoprotein-E, leptin replacement, leptin,
mild cognitive impairment.
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