Genetic engineering of human induced pluripotent stem cells has revealed very specifically how a key mutated protein is involved in familial Alzheimer's. Familial Alzheimer’s is a subset of early-onset Alzheimer's disease that is caused by inherited gene mutations.
Analysis of 40 spinal marrow samples, 20 of which belonged to Alzheimer’s patients, has identified six proteins in spinal fluid that can be used as markers for Alzheimer's. The analysis focused on 35 proteins that are associated with the lysosomal network — involved in cleaning and recycling beta amyloid. None of the six proteins had previously been linked to Alzheimer’s.
http://www.eurekalert.org/pub_releases/2013-10/lu-ast102313.php
Blocking a receptor involved in inflammation in the brains of mice with severe Alzheimer’s produced marked recovery in blood flow and vascular reactivity, a dramatic reduction in toxic amyloid-beta, and significant improvements in learning and memory.
The receptor was the bradykinin B1 receptor (B1R), and the finding confirms a role of B1R, and neuroinflammation, in the development of Alzheimer’s. It also points to a new target for therapy.
A multi-year study involving 207 healthy older adults, in which their spinal fluids were repeatedly sampled and their brains repeatedly scanned, has found that disruptions in the default mode network emerges about the same time as chemical markers of Alzheimer’s appear in the spinal fluid (decreased amyloid-beta and increased tau protein). The finding suggests not only that amyloid-beta and tau pathology affect default mode network integrity early on, but that scans of brain networks may be an equally effective and less invasive way to detect early disease.
The first detailed characterization of the molecular structures of amyloid-beta fibrils that develop in the brains of those with Alzheimer's disease suggests that different molecular structures of amyloid-beta fibrils may distinguish the brains of Alzheimer's patients with different clinical histories and degrees of brain damage.
A study involving mice lacking a master clock gene called Bmal1 has found that as the mice aged, their brains showed patterns of damage similar to those seen in Alzheimer's disease and other neurodegenerative disorders. Many of the injuries seemed to be caused by free radicals. Several key antioxidant enzymes, which usually neutralize and help clear free radicals from the brain, have been found to peak in the middle of the day in healthy mice, but not in these mice lacking Bmal1.
A new study involving 96 older adults initially free of dementia at the time of enrollment, of whom 12 subsequently developed mild Alzheimer’s, has clarified three fundamental issues about Alzheimer's: where it starts, why it starts there, and how it spreads.
Analysis of 5715 cases from the National Alzheimer's Coordinating Center (NACC) database has found that nearly 80% of more than 4600 Alzheimer's disease patients showed some degree of vascular pathology, compared with 67% of the controls, and 66% in the Parkinson's group. The link was especially strong for younger patients with Alzheimer’s.
The hippocampus is damaged early in Alzheimer’s, while the thalamus is generally unaffected until the late stages. Brain imaging of the hippocampus and the thalamus in 31 patients with Alzheimer's and 68 healthy controls has revealed increased levels of iron in the hippocampus of those with Alzheimer’s, but not in the thalamus. Moreover, this increased iron was associated with tissue damage in patients with Alzheimer's but not in the healthy older individuals.
Analyses of cerebrospinal fluid from 15 patients with Alzheimer's disease, 20 patients with mild cognitive impairment, and 21 control subjects, plus brain tissue from some of them, has found that those with Alzheimer’s had lower levels of a particular molecule involved in resolving inflammation. These ‘specialized pro-resolving mediators’ regulate the tidying up of the damage done by inflammation and the release of growth factors that stimulate tissue repair. Lower levels of these molecules also correlated with a lower degree of cognitive function.