From the Alzheimer’s world: Lim 2012 ”Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults” in Neurology today finds that amyloid plaques correlate more strongly with decline in visual memory over the succeeding 18 motnhs than does the APOE genotype. This conclusion itself isn’t so surprising — I recently heard Christopher Newton-Cheh speak about this work on SNPs associated with high blood pressure, and he pointed out that all the associated SNPs put together are less predictive of later blood pressure problems than simply checking someone’s blood pressure. It seems natural that phenotype predicts phenotype better than genotype predicts phenotype.
However, it was interesting to learn about how brain imaging for Alzheimer’s has advanced. This study was done by injecting patients with Pittsburgh compound B aka PiB:
Klunk 2004 was the first to use PiB to image Aβ deposits. The compound is injected into the patient’s bloodstream and ends up being retained in regions of the brain where Aβ plaques are present. Provided you have radiolabeled it, it can then be imaged via PET scan. Dozens of studies have since been published using this same method. It seems to be pretty well-established at this point.
This helps me understand why researchers such as Ishikawa 2006 have been searching for nontoxic compounds that can be used for imaging of prion deposits, with some success in mice. Ishikawa found some success with styrylbenzoazole derivatives, leading to the Doh-Ura lab’s later work with cpd-B. I am not clear whether that group has had any luck advancing their prion plaque imaging to human trials. It appears that the UCSF diagnostic clinical trial does not include PET scans, so it is likely that compounds to specifically image PrP deposits are still a ways from the clinic. Boxer 2007 at the Jagust lab at UC-Berkeley tried using PiB and another compound, FDDNP, to image symptomatic prion disease patients and Alzheimer’s patients. The prion patient imaged with PiB looked pretty much like the controls, whereas the patient imaged with FDDNP gave an intermediate signal, somewhere between the Alzheimer’s patients and the control. So it looks like PiB will not be useful as a diagnostic for prion disease; FDDNP may have some potential but no one seems to have done more work with it in the past five years. Boxer’s patients were two brothers with a 6-octapeptide repeat insertion in PRNP, which is generally considered to be a genetic form of CJD, though repeat insertions can sometimes give mixed CJD/GSS phenotypes (see for instance Goldfarb 1991).