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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Greenberg, S. Articles by Johnson, K. PubMed Articles by Greenberg, S. Articles by Johnson, K.

Early detection of hereditary cerebral amyloid angiopathy with PiB

¹ Massachusetts General Hospital, Boston, Massachusetts

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Objectives: Patients with advanced cerebrovascular deposition of beta-amyloid (cerebral amyloid angiopathy, CAA) show increased PiB retention in an occipital predominant pattern (Johnson, Ann. Neurol. 2007). There is no definitive proof, however, that this PiB signal represents CAA rather than accompanying Alzheimer’s disease (AD) plaque pathology.

Methods: PiB-PET, CT, MRI, and genetic testing were evaluated in a 42 year-old man with Iowa-type hereditary CAA (ICAA), a condition with severe CAA, but little or no fibrillar plaque amyloid. The subject presented clinically with a 10-year history of tremor and atypical migraine, but no dementia. Post-mortem brain from a first-degree relative with ICAA was stained with PiB. PET DVR values were compared to AD and normal control groups.

Results: Amyloid precursor protein exon 17 sequencing showed the characteristic Iowa mutation, substitution of asparagine for aspartic acid at position 23. Marked PiB retention (DVR1.8) was seen in occipital cortex, whereas regions typically involved in AD had low retention. PiB staining of post-mortem tissue showed exclusively vascular labeling, supporting the inference that the PiB-PET signal in the patient represented CAA rather than AD plaque pathology. CT demonstrated occipital calcifications characteristic of ICAA.

Conclusions: These findings offer strong evidence that PiB-PET detects vascular as well as plaque amyloid and can identify the vascular deposits as an early manifestation of CAA. Advanced cerebrovascular amyloid deposition appears to precede other manifestations of CAA such as extensive hemorrhage or white matter damage.

Research Support: This work was supported by grants from the National Institute on Aging (R01-AG026484, P50 AG00513421) and Alzheimer Association (IIRG-06-26331).

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Greenberg, S. Articles by Johnson, K. PubMed Articles by Greenberg, S. Articles by Johnson, K.