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      Axonal Transport and Alzheimer's Disease

      1 , 2
      Annual Review of Biochemistry
      Annual Reviews

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          Abstract

          In contrast to most eukaryotic cells, neurons possess long, highly branched processes called axons and dendrites. In large mammals, such as humans, some axons reach lengths of over 1 m. These lengths pose a major challenge to the movement of proteins, vesicles, and organelles between presynaptic sites and cell bodies. To overcome this challenge axons and dendrites rely upon specialized transport machinery consisting of cytoskeletal motor proteins generating directed movements along cytoskeletal tracks. Not only are these transport systems crucial to maintain neuronal viability and differentiation, but considerable experimental evidence suggests that failure of axonal transport may play a role in the development or progression of neurological diseases such as Alzheimer's disease.

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          Most cited references138

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          Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease.

          We identified axonal defects in mouse models of Alzheimer's disease that preceded known disease-related pathology by more than a year; we observed similar axonal defects in the early stages of Alzheimer's disease in humans. Axonal defects consisted of swellings that accumulated abnormal amounts of microtubule-associated and molecular motor proteins, organelles, and vesicles. Impairing axonal transport by reducing the dosage of a kinesin molecular motor protein enhanced the frequency of axonal defects and increased amyloid-beta peptide levels and amyloid deposition. Reductions in microtubule-dependent transport may stimulate proteolytic processing of beta-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease.
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            SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE

            P DAVIES (1976)
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              Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain.

              Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.
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                Author and article information

                Journal
                Annual Review of Biochemistry
                Annu. Rev. Biochem.
                Annual Reviews
                0066-4154
                1545-4509
                June 2006
                June 2006
                : 75
                : 1
                : 607-627
                Affiliations
                [1 ]Institute of Clinical Neurophysiology, Division of Neurology, University Medical Center, SI-1525 Ljubljana, Slovenia; email:
                [2 ]Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, California 92093-0683; email:
                Article
                10.1146/annurev.biochem.75.103004.142637
                16756504
                8c9a2edd-de4f-451b-b4ea-e0a7a65abaa9
                © 2006
                History

                Neurology,Health & Social care,Clinical Psychology & Psychiatry,Public health
                Neurology, Health & Social care, Clinical Psychology & Psychiatry, Public health

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