The global prevalence ofAlzheimer’s Disease (AD) has increased significantly and has a huge economicimpact. It most common form of dementia, is now representing one of the largestglobal healthcare challenges and estimated that approximate 25 million peopleworldwide suffer from this dreadful condition (Mayeux and Sano, 1999).Although, the etiology of Alzheimer’s disease and its pathophysiology is stillunclear. Accumulation of amyloid-beta (A?) in the brain is hypothesized totrigger pathogenic cascades that eventually lead to AD. Extracellular depositsof A? peptide (e.g.

in senile plaques) and intraneuronal accumulations of tauprotein (e.g. in neurofibrillary tangles) are the main histopathologicalfeatures of AD.

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A? deposits are present in the cortical gray matter, yearsbefore the onset of dementia.AD is also characterized by chronic braininflammation and the action free radicals on brain tissue has been investigatedextensively and the problem of oxidative is now considered to be one importantfactor in the progression of cognitive impairment (a hallmark of the disease).From the perspective ofoxidative stress and AD the blood-brain barrier (BBB) plays a significant role.BBB is a highly specialized endothelial cell membrane that lines the cerebralmicro-vessels (that make up about 95% of the total surface area) thatrepresents the interface between brain (neural cells) and circulating immune cells(such as leukocytes etc). Studies show that the BBB plays a critical role in themanifestation and progression of chronic inflammation during earlier stages of AD.The BBB is part of the neurovascular unit (NVU), whichis comprised of glial cell clusters, neurons and pericytes. During the onset of AD, it isobserved that there is a BBB dysfunction and this manifests as lower A? plaque clearancerates, impaired endothelial transport, changes in pericyte functions, anddecreased tight junction (TJ) integrity, activation of glial cells and neuro-inflammationthrough the recruitment of leukocytes in the brain.

As AD progresses, severalcomponents of the neurovascular unit undergo functional/morphological changesand become dysfunctional, this leads to nervous tissue detrition and cognitive deficits.In experiments using transgenic animal which had AD-like pathology, it has beenshown that circulating leukocytes can actually migrate through the endothelialcells and is known to have strong interactions with the NVU components andpotentially affecting their functionality and also their structural integrity. Various degrees of cognitive impairment(memory loss being very common) were reported to be associated with cholinergicneuronal loss in dementia cases (Bondy, 1995). Cholinergic modulation is vital functionrequired for short-term memory process and the cholinergic dysfunction can playa crucial role for short term memory deficits (Galizia, 1984). Recently, a plethoraof new evidence has suggested that the prime candidate responsible forproducing the neuronal changes mediating these cognitive deficits appeared to befree radicals and oxidative stress. Additionally, some studies have alsosuggested that deficits in cholinergic neurotransmitter systems and increasedlevels of free radicals and proinflammatory cytokines might be involved in ADneuropathogenesis.