@entity1687 ( @entity1687 ), a fatal @entity74 , is a juvenile @entity303 with @entity4085 in cerebral neurons. These abnormalities consist of tangles of tau protein, which is otherwise highly soluble and usually stabilizes the microtubules. Immunologically and ultrastructurally similar tangles are seen some decades later in @entity1 with @entity195 ( @entity195 ). There is evidence that tangle-bearing cells in both diseases show higher levels of free (i. e. filipin-positive) @entity165 than adjacent tangle-free nerve cells. The @entity165 accumulates either in a more diffuse way (mainly in @entity195 ) or in granule-like accumulations (mainly in @entity1687 ). In @entity1687 , neuron @entity165 may originate from sources other than the alimentary tract. Experiments with a @entity1687 @entity19 model revealed that even in pure neuron cultures, the @entity1687 -/- neurons accumulate free @entity165 in contrast to @entity1687 -wt littermates, suggesting that the @entity165 is either synthesized by the neurons or liberated from degenerated ones before being taken up by the endosomal/lysosomal pathway. The accumulation of free @entity165 in the somata of @entity1687 neurons is associated with a decrease of @entity165 levels in myelin sheaths. In terms of tau protein, @entity1687 -/- @entity19 exhibit higher levels of AT8-positive tau, suggesting that the phosphorylation-dependent mAb AT8 has detected a tau-epitope in a state considered to represent early stages of tangle formation. Concomitantly to the increase in free intracellular @entity165 , the rate-limiting enzyme in @entity165 and @entity12307 biosynthesis, @entity2453 reductase, was found to be significantly reduced. Experimental blockade of the enzyme's activity by application of the lipid-lowering drug lovastatin showed subcellular shifts in tau phosphorylation as monitored with mAbs AT8, 12E8 and others. In summary, the data showed interesting similarities between @entity1687 and @entity195 suggesting some pathological metabolic pathway in common.

@entity165 and tau protein--findings in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity303 :: ('MESH:D003704', 'Disease') :: ['dementia'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1687 :: ('MESH:D052556', 'Disease') :: ['Niemann Pick C', 'NPC'] @entity4085 :: ('MESH:D009081', 'Disease') :: ['massive nerve-cell loss and cytoskeletal abnormalities'] @entity12307 :: ('CHEBI:24913', 'Chemical') :: ['isoprenoid'] @entity74 :: ('MESH:D030342', 'Disease') :: ['autosomal-recessive neurovisceral lipid storage disorder'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity2453 :: ('MESH:C008047', 'Chemical') :: ['HMG-CoA'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity195 :: (MESH:D000544,Disease) :: ['Alzheimer's and Niemann Pick C's disease']
