Alzheimer's disease (AD) affects 4.5 million Americans according to the National Institutes of Aging; the direct and indirect costs of the disease exceed $100 billion each year. As the wave of baby boomers continues to age it is apparent that the number of people with AD will increase, along with the costs for care. While no one knows the precise underlying cause leading to the characteristic pathology of the disease, a new study finds that a "leaky" blood-brain barrier (BBB) — and levels of water-soluble antioxidants — may offer clues to unlocking this haunting disease.
Thirty-six participants (mean age 70 + 7 years) diagnosed with mild to moderate Alzheimer's disease (Mini-Mental Status Exam 19+5) participated in a prospective biomarker study. The evaluation of the participants included clinical assessments, brain imaging, and cerebral spinal fluid (CSF) along with plasma collection for a period of one year. The participants were evaluated at baseline, three months and 12 months. The researchers employed the CSF-albumin index to determine blood-brain barrier integrity. CSF and plasma levels of ascorbic acid (AA) and uric acid (UA) were also measured.
The researchers observed the following:
§ As expected, the concentration of AA was higher in the CSF compared to the plasma reflected by a CSF-to-plasma ratio of AA greater than 1.0 in all cases, with an average of 4.0. In contrast, the concentration of UA in the CSF was lower than plasma reflected by a CSF-to-plasma ratio of UA was less than 0.25 in all subjects.
§ The mean CSF-albumin index was 7.2. However, in 22% of the study participants, the CSF-albumin index was greater than 9.0, indicating blood-brain barrier disruption.
§ There were no correlations appreciated between plasma AA and age, gender, APOE status, MMSE at baseline or rates of clinical decline at 12 months. However, a positive correlation did exist between plasma AA and hippocampus volume at baseline and at 12 months. Study participants in the upper 25% of plasma AA at baseline showed the least temporal-lobe volume rate of decline at 12 months.
§ CSF-to-plasma AA ratio inversely correlated with hippocampus volume rate of decline and temporal-lobe volume rate of decline at 12 months. An inverse correlation between CSF-to-plasma AA ratio and CSF-albumin index, and a positive correlation between the CSF-to-plasma UA ratio and the CSF albumin index was significant.
Blood-brain barrier integrity is generally thought to be perturbed in cerebrovascular disease, but preserved in AD. Although BBB impairment is not thought to be a primary mechanism of disease it may be an important modifier of treatment and outcome.
The study found BBB impairment in a significant minority of subjects with AD. Furthermore, BBB disruption may be clinically significant by allowing antioxidants to "diffuse down" their respective concentration gradient facilitating unabated oxidative processes in the brain that underlie AD pathology. The relationship between this phenomenon, BBB impairment and maintenance, and the neurodegenerative process remains to be clarified.