New imaging agent correlates amyloid with Alzheimer’s

Positron-emission tomography in combination with the radio labeled compound florbetapir F-18 detected beta-amyloid plaques with 93% sensitivity and 100% specificity in the brains of 35 elderly patients, most of whom had some form of dementia.

The florbetapir-PET imaging could be an important diagnostic tool for Alzheimer’s disease — perhaps with the ability to detect brain plaques early in a prodromal stage of the disease — and to measure plaque changes in relation to therapeutic response in future drug studies.

The study also represents the first time an amyloid imaging agent has been tested against autopsy results. It’s really exciting to be able to correlate imaging so strongly with autopsy findings.

The study does not make it clear what specific clinical applications the imaging procedure could have, be it the clinical diagnosis of Alzheimer’s disease or the prediction of progression to dementia.

Like Pittsburg imaging compound B (PiB), florbetapir binds to beta-amyloid plaques in the living brain. PiB’s use, however, has been limited by its short half-life of 20 minutes. Florbetapir achieves maximum uptake at 30 minutes and remains unchanged for the next 60 minutes, providing a wide time window to obtain a 10-minute image.

The prospective study involved 35 patients in hospice or long-term care facilities that were expected to die within 6 months. Six of the patients were used to validate the imaging procedure while the remaining 29 were used in the primary validation study.

Among the 29 in the validation analysis, the mean age was 80 years. This group included 13 with a clinical diagnosis of Alzheimer’s, 5 with other dementias, 9 with normal cognition, and the rest with mild cognitive impairment. Their mean Mini-Mental State Examination (MMSE) score was 3.8.

The control group comprised 74 young, healthy subjects, 27 of whom were positive for the APOE e4 allele, which greatly increases the risk of developing Alzheimer’s in later life.

The control subjects had a mean age of 27 years and a mean MMSE score of 29.7. Florbetapir imaging was negative for all 74 subjects, including those with the APOE e4 allele.

Florbetapir-PET imaging in the 35 patients was significantly correlated with both immunohistochemistry and silver stain for beta-amyloid plaques in each of the six brain regions that the investigators examined (frontal, temporal, parietal, anterior and posterior cingulated, precuneus, and cerebellum).

At autopsy, 15 patients in the validation group met pathologic criteria for Alzheimer’s disease. Of these, 14 had positive florbetapir-PET scans, leading to a sensitivity of 93%.

The other 14 patients had low levels of beta-amyloid plaque on autopsy, and thus did not meet the diagnostic criteria for Alzheimer’s. All 14 also had negative glorbetapir-PET scans, giving 100% specificity.