Journal of Alzheimer's Disease - Volume 4, issue 3

Authors: Grammas, P. | Yamada, M. | Zlokovic, B.

Article Type: Research Article

Abstract: Neuronal cell death is the primary underlying pathogenic lesion in Alzheimer's disease (AD). Despite intense research efforts, the mechanisms that contribute to neuronal cell death have not been clarified. In this debate we address the question, Is AD a vascular or metabolic disorder? Here we defend the hypothesis that the cerebromicrovasculature is a key player in the pathogenesis of AD. Evidence is presented that vascular amyloid β (Aβ) is more closely associated with tau pathology than the distribution of diffuse or neuritic plaque Aβ. Furthermore, brain endothelial cells are identified as important regulators of the neuronal microenvironment, including Aβ levels. …Finally, evidence is presented that brain endothelial cells undergo cellular and biochemical changes in AD and that the release of neurotoxic factors from these dysfunctional cells contributes to the neuronal cell loss characteristic of AD. Show more

DOI: 10.3233/JAD-2002-4311

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 217-223, 2002

Authors: Blass, John P. | Gibson, Gary E. | Hoyer, Siegfried

Article Type: Research Article

Abstract: This paper discusses the hypothesis that the cerebrometabolic deficiency in Alzheimer's disease(AD) is the proximate cause of the clinical disability. Several sets of observations support this hypothesis. (1) Impaired brain metabolism essentially always occurs in clinically significant AD, and the degree of clinical disability is proportional to the degree of metabolic impairment. The earliest, mildest changes in brain metabolism occur even before the onset of measurable cognitive impairment or atrophy. This observation disproves the now outdated assumption that the decreased metabolism is simply a consequence of decreased mental function or of atrophy. One of the important mechanisms reducing brain metabolism …in AD appears to be damage to key mitochondrial components. Another appears to relate to inappropriate responses to insulin, i.e. to diabetes of the brain. (2) Inducing impairments of brain metabolism causes changes in mentation that mimic the clinical disabilities in AD, in both humans and experimental animals. (3) Preliminary results from several units suggest that treatment directed at the impairment of brain metabolism can improve neuropsychological functions in AD patients. The hypothesis presented here in no way negates the importance of other mechanisms in AD, such as amyloid accumulation, vascular compromise, and free radical action. However, those other abnormalities including amyloidosis can occur in people whose mentation is still clinically unimpaired. In contrast, once significant decrease in the rate of brain metabolism occurs, mentation becomes defective. Show more

DOI: 10.3233/JAD-2002-4312

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 225-232, 2002

Authors: Iqbal, Khalid | Grundke-Iqbal, Inge

Article Type: Research Article

DOI: 10.3233/JAD-2002-4313

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 235-238, 2002

Authors: Blass, John P.

Article Type: Research Article

DOI: 10.3233/JAD-2002-4314

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 241-242, 2002

Authors: Herrup, Karl | Arendt, Thomas

Article Type: Research Article

DOI: 10.3233/JAD-2002-4315

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 243-247, 2002

Authors: Bowser, Robert | Smith, Mark A.

Article Type: Research Article

DOI: 10.3233/JAD-2002-4316

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 249-254, 2002

Authors: Morgan, Dave | Keller, R. Kennedy

Article Type: Research Article

DOI: 10.3233/JAD-2002-4317

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 257-260, 2002