Abstract
Background
Mutation in the presenilin-1 (PS-1), presenilin-2 (PS-2), or amyloid precursor protein (APP) genes results in autosomal dominant Familial Alzheimer's disease (FAD), in which the onset of the disease occurs at an unusually early age (onset under the age of 60). Previously, androgen modulating therapy for AD has been proposed by our group based on published animal and clinical studies. We present a case report on a symptomatic FAD mutation carrier (PS-1) prior to and following testosterone intervention therapy.
Methods
We investigated clinical and blood biomarker correlates in this female aged 32 years. She underwent comprehensive neuropsychological and blood biomarker testing. We monitored blood plasma levels of amyloid beta 1-42, amyloid beta 1-40, clusterin, total apoE and TNF-alpha during the course of this treatment.
Results
Neuropsychological testing revealed a Mini-Mental State Examination (MMSE) of 17 and severely impaired working and episodic memory, as examined by Rey Auditory Verbal Learning test (RAVLT). Analysis of a panel of biomarkers before treating with testosterone implant at two different time points (3 weeks apart) showed amyloid beta 42 (97.52 pg/ml; 115.43pg/ml), amyloid beta 40 (148.87 pg/ml; 136.17 pg/ml), total apoE (18.5 mg/dl; 11.5 mg/dl), clusterin (450.21 μg/ml; 453.10 μg/ml), and TNF-alpha (28.6 pg/ml; 38.08 pg/ml). A repeated analysis of the same panel of biomarkers was then carried out one month after treatment with 200mg of testosterone pellet implant. Testing revealed a MMSE score of 18 and constant memory performance. Plasma biomarkers showed amyloid beta 42 (87.13 pg/ml), amyloid beta 40 (155.46 pg/ml), total apoE (12.5 mg/dl), clusterin (420.34 μg/ml), and TNF-alpha (10.86 pg/ml).
Conclusions
From our results it appears that amyloid beta 42/40 ratio, clusterin and TNF-alpha levels have significantly decreased after one month of testosterone treatment (P < 0.01). Total apoE levels showed an increase (p < 0.05) in response to treatment. These promising preliminary findings require longer follow up and investigation in additional patients before a definite decision can be reached on the clinical significance of this therapeutic approach.