. . . and today, three news morsels:
First, sleep: Researchers at UCSF led by Jun Yeop Oh sought correlations between loss of specific areas of brain cells in the autopsies of 12 people with Alzheimer’s and 10 with PSP who during life had had detailed sleep studies. They found relationships between several specific abnormalities of sleep with loss of neurons in two clusters of cells in the hypothalamus that use orexin and histamine, respectively, as their neurotransmitters. A third area known to be related to sleep, the (dopamine-using) locus ceruleus in the midbrain, showed little or no such correlation. The authors conclude that this line of inquiry “is crucial in designing the next generation of sleep medications [by boosting orexin or histamine] and even slowing down the progress of neurodegenerative disease through early interventions.”
Next, tau: A report from Michela Marcatti and colleagues at University of Texas Medical Branch in Galveston describes important differences between Alzheimer’s and PSP in the way their abnormal tau acts on the brain’s synapses. They specifically looked at soluble oligomers – clumps of only a few tau molecules that remain soluble in the brain’s fluids, making them far more toxic than the larger, insoluble neurofibrillary tangles. They found that in AD, tau oligomers displace beta-amyloid oligomers from the synapses after the initial disease stages, which may explain why treatments aimed at beta-amyloid have failed to date. This bolsters our hopes AD and PSP could share a common treatment. The authors also suggest that the various tau oligomers’ different patterns of attack on the synapses might explain the different subtypes of PSP.
Finally, a new drug: The oral drug AZP2006 is presently in a clinical trial for PSP in Europe. It acts by enhancing the effect of progranulin, a protein involved in multiple cell processes with potential relationships to neurodegeneration. Researchers at Alzprotect, the French drug company sponsoring the trial, published the effects of AZP2006 in cultures of rat brain cells (neurons and microglia together) and in mice that had been genetically engineered to age quickly. It reduced abnormal tau phosphorylation and inflammation in the cultures and slowed the rate of cognitive decline in the mice. It actually restored some of the animals’ lost cognitive abilities (!!), but we don’t know how long that benefit would last or if it resulted from rescue of sick cells or from some more ordinary drug action.