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(Stroke. 2003;34:335.)
© 2003 American Heart Association, Inc.

Advances in Stroke 2002

Converging Pathogenic Mechanisms in Vascular and Neurodegenerative Dementia

Costantino Iadecola, MD Philip B. Gorelick, MD, MPH, FACP

From the Division of Neurobiology (C.I.), Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, and Center for Stroke Research (P.B.G.) Department of Neurologic Sciences, RUSH Medical Center and RUSH Medical College, Chicago, Ill.

Correspondence to C. Iadecola, MD, Division of Neurobiology, Weill Medical College of Cornell University, 411 E 69th St, KB410, New York, NY 10021. E-mail coi2001@med.cornell.edu

Key Words: Alzheimer disease • cognitive disorders • stoke • vascular reactivity

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Dementia is a common neurological syndrome with a major impact on the health and quality of life of the elderly. Although the causes of dementia are numerous, Alzheimer dementia (AD) and vascular dementia (VaD) are responsible for most cases.¹ Recent basic and clinical investigations have provided evidence that AD and VaD, traditionally considered distinct clinical and pathophysiological entities, may share common features. In this brief review, we will present these advances and a synthesis, focusing on the impact that this new information may have on the diagnosis and treatment of these conditions.

Alzheimer Dementia

The neuropathology of AD is characterized by ß-amyloid deposition in brain parenchyma and blood vessels and by neurofibrillary tangles.² The Aß peptide derives from a larger protein, the amyloid precursor protein (APP), that is cleaved by the proteases and ß secretases to produce Aß1-40 and Aß1-42.² In familial forms of AD, mutations in the APP or presenilin genes promote amyloidogenic APP cleavage, leading to increased Aß production.² Present models of AD advocate that Aß accumulation in the tissue produces the neuronal dysfunction and death that underlies the dementia.³ However, the mechanisms by which Aß produces neuronal dysfunction have not been elucidated in full. Although Aß is well-known to be cytotoxic,^4–6 recent findings in transgenic mice overexpressing APP have demonstrated that Aß also has profound effects on cerebrovascular regulation. Resting cerebral blood flow (CBF) is reduced in regions of the cerebral cortex and in the hippocampus of APP mice.⁷ The cerebral vessels of these mice do not respond to . . . [Full Text of this Article]

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