While everyone agrees that amyloid-beta protein is part of the problem, not everyone agrees that amyloid plaques are the cause (or one of them) of Alzheimer’s. Other forms of amyloid-beta have been pointed to, including floating clumps called oligomers or ADDLs. A new study, using mice engineered to form only these oligomers, and never any plaques, throughout their lives, provides more support for this theory. Mice that never developed plaques were just as impaired by the disease as mice with both plaques and oligomers, and when a gene that converted oligomers into plaques was added to the mice, the mice were no more impaired than they had been before. This may explain why treatments aimed at removing plaques have not been successful, and offers a new approach to the treatment of Alzheimer’s.
Alzheimer's memory problems originate with oligomers not plaques
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Brain network decay detected in early Alzheimer's
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.
Inflamed iron-containing cells found in Alzheimer's brains
A post-mortem study of five Alzheimer's and five control brains has revealed the presence of iron-containing microglia in the subiculum of the Alzheimer's brains only. The subiculum lies within the hippocampus, a vital memory region affected early in Alzheimer's. None of the brains of those not diagnosed with Alzheimer's had the iron deposits or the microglia, in that brain region, while four of the five Alzheimer's brains contained the iron-containing microglia.
Impaired waste management in the brain a cause of Alzheimer's?
Aging linked to impaired garbage collection in the brain
A mouse study has shown that, as cells age, their ability to remove damaged proteins and structures declines.
The process of waste management, called autophagy, involves a component within the cell (an autophagosome) engulfing misfolded proteins or damaged structures (putting them in a garbage bag, essentially). The autophagosome then fuses with a second cellular structure, called a lysosome, that contains the enzymes needed to breakdown the garbage, allowing the components to be recycled and reused.
Blood-clotting protein implicated in cognitive decline and Alzheimer's
Alzheimer's disease is associated with abnormalities in the vast network of blood vessels in the brain, but it hasn’t been known how this affects cognition. A study has now shown that a blood-clotting protein called fibrinogen plays a part.
The study found that fibrinogen, after leaking from the blood into the brain, activates the brain's immune cells and triggers them to destroy synapses, which are critical for neuronal communication.
Tau protein travels with neuronal signals
Tau protein stabilizes structures that transport supplies from the center of the cell to the extremities, but sometimes some tau is not bound to these microtubules and instead clumps together into neurofibrillary tangles — one of the hallmarks of Alzheimer's disease, and also linked to other neurodegenerative disorders. A new study supports the theory that ‘bad’ tau travels to different brain regions via the synapses — that is, it’s secreted with the signals passing between neurons.
Where Alzheimer's starts and how it spreads
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.
Blocking inflammation receptor helps Alzheimer's mice
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.
Alzheimer's disease consists of 3 distinct subtypes
A two-year study which involved metabolic testing of 50 people, suggests that Alzheimer's disease consists of three distinct subtypes, each one of which may need to be treated differently. The finding may help explain why it has been so hard to find effective treatments for the disease.
The subtypes are:
New mechanism adds to understanding of Alzheimer's causes
New findings identify a mechanism that accelerates aging in the brain and gives rise to Alzheimer's disease.
The findings center on “enhancers”, which turn the activity of genes up or down based on influences like aging and environmental factors. Comparing enhancers in brain cells of people at varying stages of Alzheimer's and healthy people has revealed that in normal aging, there is a progressive loss of important epigenetic marks on enhancers. This loss is accelerated in the brains of people with Alzheimer's.
Brain changes linked with Alzheimer's years before symptoms appear
A very long-running study involving 290 people at risk of Alzheimer's has found that, in those 81 people who developed MCI or dementia, subtle changes in cognitive test scores were evident 11 to 15 years before the onset of clear cognitive impairment. They also showed increases in the rate of change of tau protein in cerebrospinal fluid an average of 34.4 years (for t-tau, or total Tau) and 13 years (for a modified version called p-tau) before the beginning of cognitive impairment.
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