http://www.ncbi.nlm.nih.gov/pubmed/19906263 LINK Late-onset Alzheimer's disease (LOAD) is the most common cause of late-onset dementia in western societies. Despite remarkable achievements in human genetics throughout the years, in particular technological advances in gene mapping and in statistical methods that relate genetic variants to disease, to date only a small proportion of the genetic contribution to LOAD can be explained leaving several remaining genetic risk factors to be identified. A possible explanation for the difficulty in gene identification is that LOAD is a multifactorial complex disorder with both genetic and environmental components. Multiple genes with small effects each ("quantitative trait loci"[QTLs]) are likely to contribute to the quantitative traits associated with the disease, such as memory performance, amyloid/tau pathology, or hippocampal atrophy. The motivation for identifying the genetics of LOAD is clear. Not only could it shed light on disease pathogenesis, but it may also provide potential targets for effective treatment, screening, and prevention. Here, we review the usefulness of genetic variation as diagnostic tools and biomarkers in LOAD and discuss the potentials and difficulties researchers face in designing appropriate studies for gene discovery. |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825106/?tool=pubmed LINK Imaging of patients with Alzheimer's Disease (AD) have allowed for
quantitative exploration of the natural history of amyloid deposition
and it's relationship to neurodegeneration. Amyloid imaging also shows
significant promise in differential diagnosis of mild cognitive
impairment or atypical dementias. However, amyloid detection may be of
greatest utility in healthy elderly in whom amyloid imaging has
confirmed prior autopsy reports of a significant percentage of
asymptomatic adults with Alzheimer's pathology. Understanding the
relationship between this pathology and future cognitive status has
significant implications for the application of disease modifying
medications in the ‘pre-clinical’ phase of disease. Given the
considerable clinical experience compared to other tracers, the current
review focuses on the literature involving Pittsburgh Compound-B (PiB)
PET. FOR LINK TO PETSCANS.info, please click here: PETSCANS.info |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749087/?tool=pubmed LINK Molecular chaperones and heat shock proteins (Hsp) have emerged as critical regulators of proteins associated with neurodegenerative disease pathologies. The very nature of the chaperone system, which is to maintain protein quality control, means that most nascent proteins come in contact with chaperone proteins. Thus, amyloid precursor protein (APP), members of the gamma-secretase complex (presenilin 1 [PS1] collectively), the microtubule-associated protein tau (MAPT) as well as a number of neuroinflammatory components are all in contact with chaperones from the moment of their production. Chaperones are often grouped together as one machine presenting abnormal or mutant proteins to the proteasome for degradation, but this is not at all the case. |
