Andre Delacourte on Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship.
COMMENT My only comment is to emphasize the importance of the 'AND' in the last sentence.
80 RESULTS
COMMENT My only comment is to emphasize the importance of the 'AND' in the last sentence.
COMMENT Because all therapeutic trials based on the amyloid cascade are, up to now, failures, all other hypotheses are welcome. Especially if they able to generate new potential anti-Alzheimer drugs. 0 andre.delacourte
COMMENT This paper corroborates neuropathological findings: amyloid deposition can be found in non-demented patients. Correlation with cognitive deficits comes with intensification of amyloidosis and, most importantly, the extension of tau pathology. Question: wh
COMMENT This does not explain why you can find huge Abeta deposition in the brain of non-demented people. Why is it that scientists are more impressed by mouse models than human physiopathology? An alternative explanation for the amyloid cascade hypothesis of neu
COMMENT This paper confirms that very early onset FAD is generally clinically atypical. Note that these patients were affected by a full-blown tauopathy, unfortunately poorly documented in the paper. One can guess that the specific clinical features are essential
COMMENT After plaques, protofibrils, Aβ42, it is suggested that the killer is the dimer. How can we reconcile this in vitro finding with neuropathological observations of non-demented patients with widespread and huge Aβ aggregates (not plaque cores) in the neoco
COMMENT These results fit well with our brain bank data: hippocampal tangles are always observed in aging, more or less. With amyloidosis, there is a development of the basic tauopathy, leading to Alzheimer disease. 0 andre.delacourte Nonoverlapping but synergeti
COMMENT Cortical amyloid deposition is almost constant in sporadic Lewy body disease. References: Deramecourt, JNEN, 2006 0 andre.delacourte
COMMENT The idea is sound, but neuritic dystrophy means that there is a tauopathy. For Aβ oligomers that would interfere with LTP, because amyloid deposits are numerous before any significant cognitive impairment, why don't we observe LTP-related defects? Or
COMMENT In other words, sporadic tauopathy and synucleinopathy are fueled by APP dysfunction. These observations are in good agreement with ours. 0 andre.delacourte Biochemical staging of synucleinopathy and amyloid deposition in dementia with Lewy bodies.
COMMENT Tau is a MAP and indirectly a thermometer, modified by temperature, stress, hypo- or hypermetabolism, etc. This is an interesting paper showing that modeling tauopathy for AD studies is tricky. 0 andre.delacourte
COMMENT Based upon neuropathological and biochemical observations of the human brain, a relevant model of Alzheimer pathology should present a synergy between tauopathy and amyloidosis. The model presented here sounds good. 0 andre.delacourte Nonoverlapping but s
COMMENT I understand here that antibodies enter the brain, but not necessarily the neurons, and that immunotherapy here works for extracellular tangles, reducing part of the late-event burden. But does the immunotherapy work on the intracellular pathological fact
COMMENT These findings suggest more a loss of function of APP/AICD than a gain of toxic function, since there is no correlation between the precise early distribution of amyloid and clinical impairment. 0 andre.delacourte
COMMENT Results on our brain bank are in good agreement with this interesting study. References: Delacourte et al, Neurology, 2002 0 andre.delacourte