Blood-brain barrier impairment in Alzheimer disease: stability and functional significance

Neurology. 2007 May 22;68(21):1809-14. doi: 10.1212/01.wnl.0000262031.18018.1a.


Objective: To determine the stability and functional significance of blood-brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD).

Methods: Thirty-six patients (mean age 71 +/- 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 +/- 5) participated in a biomarker study involving clinical assessments, brain imaging, and CSF and plasma collection over 1 year. BBB integrity was assessed with the CSF-albumin index (CSF-AI).

Results: BBB disruption was present in an important subgroup of patients (n = 8/36, 22%) at all time points measured. CSF-AI was highly reproducible over 1 year with an intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived white matter hyperintensity, body mass index) were not strongly associated with CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a manner indicating that peripheral IgG has greater access to the CNS in patients with an impaired BBB. Further evidence for the physiologic significance of the CSF-AI was noted in the form of correlations with rates of disease progression, including annual change on MMSE (r(2) = 0.11, p = 0.023), annual Clinical Dementia Rating sum-of-boxes change (r(2) = 0.29, p = 0.001), and annual ventricular volume change (r(2) = 0.17, p = 0.007).

Conclusions: Blood-brain barrier (BBB) impairment is a stable characteristic over 1 year and present in an important subgroup of patients with Alzheimer disease. Age, gender, APOE status, vascular risk factors, and baseline Mini-Mental State Examination score did not explain the variability in BBB integrity. A role for BBB impairment as a modifier of disease progression is suggested by correlations between CSF-albumin index and measures of disease progression over 1 year.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aged
  • Albumins / cerebrospinal fluid*
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / physiopathology
  • Apolipoproteins E / genetics
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / physiopathology*
  • Body Mass Index
  • Brain / blood supply
  • Brain / pathology
  • Brain / physiopathology*
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / diagnosis
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Hypertension / complications
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology
  • Predictive Value of Tests
  • Risk Factors
  • Sex Factors


  • Albumins
  • Apolipoproteins E
  • Biomarkers