Journal of Alzheimer's Disease - Volume 9, issue s3

Authors: Perry, George | Avila, Jesús | Kinoshita, June | Smith, Mark A.

Article Type: Editorial

DOI: 10.3233/JAD-2006-9S301

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 1-1, 2006

Authors: Ballenger, Jesse F.

Article Type: Research Article

Abstract: The history of Alzheimer's disease (AD) is typically formulated as the history of great doctors and scientists in the past making great discoveries that are in turn taken up by great doctors and scientists in the present – all sharing the aim of unraveling the mysteries of the disease and discovering how it can be prevented or cured. While it can certainly be edifying to study the "great men" and how their contributions laid the foundation for current work, there are problems with this approach to history. First, it oversimplifies the actual historical development of science. Second, using history to …legitimate the present can keep us from asking critical questions about the aims and limits of contemporary research. This chapter urges a broader view of the history of AD, one that recognizes that context is as important as the great doctors to the historical development of the concept of AD. Thought of this way, I argue that it is useful to divide of the history of AD into three periods. First there was the period in which Alzheimer and Kraepelin laid the clinical and pathological foundations of the disease concept. Then there is our own period, which began in the late 1970s and has emphasized the biological mechanisms of dementia. In between, there is the period – almost completely ignored in most histories of AD – that conceptualized dementia in psychodynamic terms. It is true that the psychodynamic model of dementia did not directly contribute to the concepts and theories that dominate AD research today. But it did change the context of aging and dementia in important ways, without which AD could not have emerged as a major disease worthy of a massive, publicly supported research initiative. Show more

DOI: 10.3233/JAD-2006-9S302

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 5-13, 2006

Authors: Lage, José Manuel Martínez

Article Type: Research Article

Abstract: As we commemorate the first centennial since Alzheimer's disease (AD) was first diagnosed, this article casts back into the past while also looking to the future. It reflects on the life of Alois Alzheimer (1864–1915) and the scientific work he undertook in describing the disorder suffered by Auguste D. from age 51 to 56 and the neuropathological findings revealed by her brain, reminding us of the origin of the eponym. It highlights how, throughout the 1960's, the true importance of AD as the major cause of late life dementia ultimately came to light and narrates the evolution of the concepts …related to AD throughout the years and its recognition as a major public health problem. Finally, the article pays homage to the work done by the Alzheimer's Association and the research undertaken at the Alzheimer's Disease Centres within the framework of the National Institute on Aging (NIA) Program, briefly discussing the long road travelled in the fight against AD in the past 25 years and the scientific odyssey that we trust will result in finding a cure. Show more

DOI: 10.3233/JAD-2006-9S303

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 15-26, 2006

Authors: Ball, Melvyn J.

Article Type: Research Article

Abstract: In the absence of any naturally occurring animal model of Alzheimer's disease (AD), the British conviction in the 1970's that clinicopathological investigations of human cases offered the best approach to unraveling the pathogenesis of AD rapidly influenced clinical neuroscientists, neuropathologists and funding agencies in Canada and the USA. But as with my confreres, years of our quantifying AD lesions in autopsy brains have yet to yield definitive conclusions about what is the most important neuronal abnormality. However, during my elusive search, evidence has been slowly gathered that reactivation of latent Herpes simplex virus, traveling from trigeminal ganglia into neighbouring mesial …temporal cortex, might best explain the limbic predilection for and earliest site of neurofibrillary tangle formation. This maturing hypothesis may serendipitously prove to have been a more essential byproduct of generating the voluminous data than all the publications from our laboratory that reflected endless hours of quantitative morphometry. Show more

Keywords: Alzheimer's disease, morphometry, neurofibrillary tangles, Herpes simplex virus, hippocampus

DOI: 10.3233/JAD-2006-9S304

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 29-33, 2006

Authors: Braak, Heiko | Rüb, Udo | Schultz, Christian | Tredici, Kelly Del

Article Type: Research Article

Abstract: Alzheimer's disease (AD) and sporadic Parkinson's disease (PD) are the most frequently occurring degenerative illnesses of the human nervous system. Both involve multiple neuronal systems, but only a few types of nerve cells are prone to develop the disease-associated intraneuronal alterations. In AD affected neurons produce neurofibrillary tangles and neuropil threads, while in PD they develop Lewy bodies and Lewy neurites. In both illnesses select types of projection cells that generate long, unmyelinated or sparsely myelinated axons are particularly susceptible. This kind of selective vulnerability induces a distinctive lesional pattern which evolves slowly over time and remains remarkably consistent across …cases. In the present review, lesions developing in the cerebral cortex are described against the backdrop of the internal organisation and interconnectivities linking involved cortical areas and subcortical nuclei. In AD, six and in PD, three stages can be distinguished, reflecting the predictable manner in which the proteinaceous intraneuronal inclusions spread through the cerebral cortex. In AD stages I–II and in PD stage 4, the pathological process makes inroads into the anteromedial temporal mesocortex, entorhinal allocortex, and Ammon's horn; thereafter, in AD stages III–IV and in PD stage 5, it proceeds into the adjoining high order association areas of the basal temporal neocortex. In AD stages V–VI and in PD stage 6, the damage affects additional neocortical association areas including first order association areas and eventually extends into the primary areas of the neocortex. The gradually evolving lesional pattern in AD and PD mirrors the ground plan of the cerebral cortex. The highest densities of lesions occur in the anterior mesocortical transitional zone between allo- and neocortex. From there, the involvement diminishes by degrees and extends into both the hippocampal formation and the neocortex. The severity of the neocortical lesions decreases in inverse proportion to the trajectories of increasing cortical differentiation and hierarchical refinement. Show more

DOI: 10.3233/JAD-2006-9S305

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 35-44, 2006

Authors: Ghetti, Bernardino

Article Type: Research Article

Abstract: The invitation to participate in the commemorative issue celebrating the 100th anniversary of Dr. Alois Alzheimer's report on the disease that would later bear his name has evoked memories of my early experiences in the study of dementia, my teachers, my role-models, my aspirations and my accomplishments. Early in my career, I was fascinated with the study of hereditary neurological disorders. The observation of families in which dementia was inherited in an autosomal dominant pattern excited my scientific curiosity. Three very different phenotypes in patients from three separate families have been the basis for novel scientific discovery, which has taken …place over the past 30 years. This could not have taken place without the help of many generous patients and their families as well as wonderful colleagues for whom I am deeply grateful. Some of the original observations in these families have led to the discovery of genetic mutations in three genes that are among the most commonly affected in hereditary dementia. The work on these families has enriched the scientific community and our knowledge of dementing illnesses. Show more

DOI: 10.3233/JAD-2006-9S306

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 45-52, 2006

Authors: Hirano, Asao | Iida, Maki

Article Type: Research Article

Abstract: Argentophilic neurofibrillary tangles were described in the cerebral cortex of Alzheimer's disease and later in the pigmented neurons in the brain stem of postencephalitic parkinsonism. In 1961, wide distribution of Alzheimer's neurofibrillary tangles in the central nervous system was observed in endemic fatal neurodegenerative diseases affecting the native Chamorro population on Guam: amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam. Abundant neurofibrillary tangles were found but no senile plaques. A topographic analysis of tangles in cases inGuam and at Montefiore were published in 1962 [23]. Thereafter, Alzheimer's neurofibrillary changes were documented in various areas of the nervous system of many …other diseases. This communication is a brief review of the topographic investigation of Alzheimer's neurofibrillary changes. Occurrence of tangles in various conditions seems to indicate that various pathological agents can induce tangles. On the other hand, Alzheimer's neurofibrillary tangles, in general, show a rather striking predilection to affect particular neurons in the involved regions. Show more

Keywords: Alzheimer's disease, Alzheimer's neurofibrillary changes, parkinsonism-dementia complex on Guam, topographic study

DOI: 10.3233/JAD-2006-9S307

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 53-60, 2006

Authors: Jellinger, Kurt A.

Article Type: Research Article

Abstract: A retrospective clinico-pathological study of a consecutive autopsy series of 1050 elderly demented individuals (mean age 83.4 ± 6.0 years; MMSE < 20) was performed. Clinical diagnoses were probable or possible Alzheimer disease (62.9%), nonspecific degenerative dementia (10.4%), vascular dementia (10%), Parkinson disease with dementia (9.5%), 1.5% mixed dementia, and 5.7% other disorders. At autopsy, 86% revealed Alzheimer-related pathology, but only 42.8% showed "pure" Alzheimer disease, with additional cerebrovascular lesions in 22.6% and Lewy body pathology in 10.8%, while among 660 cases of clinically suspected Alzheimer disease, Alzheimer pathology was seen in 93%, only 44.7% in "pure" form, and additional …vascular lesions and Lewy bodies in 27.7 and 10%, respectively. The non-Alzheimer cases included Huntington and Creutzfeldt-Jakob disease, frontotemporal dementias, and others. These and other recent data indicate that in patients with the clinical diagnosis of Alzheimer disease its combination with cerebrovascular lesions and Lewy body pathologies is rather frequent. Comparison of clinical and postmortem diagnoses revealed postmortem confirmation of Alzheimer disease in 93%, of mixed and vascular dementia in 60 and 52.3%, respectively. 78% of clinically suspected degenerative dementias were pathologically definite Alzheimer disease, while in the clinical Parkinson + dementia group dementia with Lewy bodies accounted for 35%, Parkinson+Alzheimer disease, and "pure" Alzheimer disease for 29%, each. A sample of 207 prospectively studied elderly showed significant negative correlation between the preterminal psychostatus assessed by MMSE and the neuritic Braak stages, with a broad "gray" zone of Alzheimer lesions in mildly to moderately demented subjects. Similar relations between CDR and Braak stages were seen in very old subjects. The present study and the results of other recent series indicate increasing agreement between clinical and autopsy diagnoses in demented aged individuals with variable accuracy rates for different forms of dementia disorders. Show more

Keywords: Dementia disorders, Alzheimer disease, clinico-pathological correlations, diagnostic accuracy rates

DOI: 10.3233/JAD-2006-9S308

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 61-70, 2006

Authors: Kidd, Michael.

Article Type: Research Article

Abstract: The original recognition of the paired helical filaments is discussed and amplified. The original description of what are now the neuropil threads is mentioned. The ensuing importance of both these structures is emphasised and a morphology-based hypothesis of the development of the disease from the original stimuli is offered.

Keywords: Paired helical filaments, Alzheimer disease, neuropil threads, tau

DOI: 10.3233/JAD-2006-9S309

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 71-75, 2006

Authors: Esiri, M.M. | Chance, S.A.

Article Type: Research Article

Abstract: Two principal findings in the Pearson et al. paper [73] are commented on here. The first is the regional selectivity within the cerebrum of neurofibrillary tangle (NFT) formation in Alzheimer's disease (AD) which targets association cortex and the primary olfactory cortex alone among regions of primary sensory cortex. The second finding is the clustering of NFT in columns of supra- and infra-granular layers of association cortex. We review recent evidence confirming these findings and comment on their possible significance. We consider that the most attractive hypothesis to explain the vulnerability of the olfactory system and association cortex is the persistent …neural plasticity of these regions. On this basis there would be no need to postulate a progressive spreading process. The columnar distribution of clustered NFT can be well understood in the context of recent concepts of columnar organization of the cerebral cortex. The original interpretation that this distribution of NFT reflects pathology in neurons subserving cortico-cortical and cortico-subcortical connections seems to us to have stood the test of time. Show more

Keywords: Alzheimer's disease, olfactory system, neocortex, cortical minicolumns, neural plasticity

DOI: 10.3233/JAD-2006-9S310

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 79-89, 2006