In this respect, it has been recently suggested that at equal amyloid plaque loads the difference between demented and non-demented individuals lies upon the higher amount of Ab oligomers in the former relative to the latter. The incidence of NFT formation increases with age, and the difference between demented and non-demented subjects is mainly due to greater tangle densities and the spread of tangles across the neocortex in AD. Likewise, we found that the NFT score was very low in non-demented MA subjects which was matched by a Braak stage of I, while in the OO, without the symptoms of dementia and without amyloid deposits, the NFT scores reached an intermediate average value of 5.8 with Braak scores of III�CIV. The NFT score was not used for the selection of study subjects. Taken together these Dropropizine observations suggest that in humans the presence of amyloid plaques does not precede or is necessary for the development of NFT. Limited NFT deposition is consistent with normal aging and is either tolerable or perhaps serving as an adaptive/rescue event to preserve cytoskeletal integrity and axonal transport patency or involved in the management of hazardous waste resulting from damaged organelles. Supporting the changes in microcirculation, hemodynamic assessments using transcranial Doppler ultrasound demonstrated Vitamin C significantly altered measures in AD, in terms of mean flow velocities and pulsatility indices, when compared to non-demented control subjects. Along this topic, degenerated string capillaries were elevated in OO-AD, implying greater microvascular dysfunction, when compared to septuagenarian and nonagenarian non-demented groups. Intriguingly, APOE e4 carriers had significantly higher string vessel counts than nonAPOE e4 carriers. However, whether these changes are primary or secondary is unknown. In addition, the OO-AD brains revealed a severe depletion of vasoactive cholinergic and noradrenergic fibers when compared to non-demented controls, potentially resulting in loss of cerebral blood flow control.Incidentally, selective depletion of cholinergic cells of the nucleus basalis magnocellularis in rabbits induces cortical cholinergic deafferentation that results in Ab deposition in the microvessels of the cerebral cortex.