Alzheimer Disease Update 2000
The editors have collected a series of reviews, original contributions, and observations covering important new advances in Alzheimer disease. Many major and important topics in this rapidly evolving field are covered and catch the positive spirit of development in our understanding of the biology of this complex neurodegenerative disorder. Basic mechanisms of the disease process, clinical correlations, neuropathologic insights, and hypotheses for therapy are all included in this series.—Roger N. Rosenberg, MD, Editor
McGeer and McGeerArticle pioneered our current approach to inflammation and oxidative stress in Alzheimer disease and other neurodegenerative disorders. They provide us with an update in their current thinking on this subject and speculate about future therapies.
Wolozin and BehlArticle develop a common theme of protein aggregates as a primary disease initiating event in Alzheimer disease, Parkinson disease, Pick disease, Huntington disease, and other neurodegenerative disorders. This unifying approach suggests a basic common ideology underlying their causation which may be the production of hyperoxygen and free radicals. Their review is provocative and important.
Wolozin and BehlArticle have provided a concise review of the genetic program of caspases that has emerged as an important mechanism of cell death in Alzheimer disease. The caspases cascade as described offers specific targets for potential therapy in Alzheimer disease.
Elias and colleagues Article define the preclinical phase of Alzheimer disease, which may precede probable Alzheimer disease by many years. Specific measures of retention of information and abstract reasoning are useful predictors of disease.
Editorial comment by Mayeux and Small is included.Article
Shepherd et alArticle emphasize that Alzheimer disease inflammation seems to be related to tau neuritic pathology. Reduced tau neuritic pathology in Lewy body dementia correlates with significantly less inflammation. Therapeutic strategies will be influenced by these findings.
Editorial comment by Honig is included.Article
Ganguli et alArticle provide a cross-national comparison between large US and Indian population samples of apolipoprotein E4 (APOE 4) and Alzheimer disease (AD). The prevalence of AD was quite low in India, although APOE4 was associated with AD at a similar risk level. Analysis of AD in different ethnic and cultural groups provides an important perspective on the biology of the disorder.
Halliday et alArticle found that long-term use of inflammatory medications in the patients with Alzheimer disease examined enhanced cognitive performance, but did not alter the progression of Alzheimer disease brain pathology. These studies do suggest alternative hypotheses for mechanisms of cognitive improvement with nonsteroidal inflammatory agents outside of improvement in classic Alzheimer disease neuropathology. Theirs is a unique and interesting insight.
Small and colleaguesArticle describe the longitudinal preclinical phase of Alzheimer disease in which deficits in memory performance are most common and remain stable right up until the time of when a dementia diagnosis can be made. The subtly of early beginnings of Alzheimer disease need a clear definition to justify potential early therapies.
Hock et alArticle describe decreased levels of brain-derived neurotrophic factor in Alzheimer disease–affected brain, which may contribute to degeneration of specific neuronal populations including the basal forebrain cholinergic system. Levels of neural growth factor were significantly elevated in Alzheimer disease. These findings are of great interest as possible issues in neuronal degeneration in specific Alzheimer disease–affected brain regions.
Wilson et alArticle describe a series of patients with Alzheimer disease in which progressive worsening of parkinsonism is strongly associated with cognitive decline. Rates of change in parkinsonism in cognitive function were strongly correlated. The clinician needs to be aware that progressive parkinsonism in Alzheimer disease may signal an increasing rate of cognitive decline.
Hirono and colleaguesArticle have conducted single photon emission computed tomography studies in patients with dementia and find an association between aggression and decreased perfusion in the left anterior temporal cortex. They provide a quantitative assessment of reduced neuronal function as a correlate of specific behavioral deficits.
Olichney and colleaguesArticle show that cerebral amyloid angiopathies confer a greater risk of cerebrovascular lesions in Alzheimer disease, and they are probably important in producing the common entity of "mixed" Alzheimer disease/vascular dementia. Amyloid deposition is not innocent both in brain and in brain blood vessels.
Marson and colleaguesArticle provide a highly useful assessment showing financial incapacity is already significantly impaired in mild Alzheimer disease. Using their financial capacity instrument, they are able to follow the progression of disease and offer the index as an instrument in guiding financial considerations in the overall assessment of patients with Alzheimer disease.
Murrell and colleaguesArticle describe a family with a novel mutation in the amyloid precursor protein gene (V717L). Sequencing exon 17 of the amyloid precursor protein gene revealed a single nucleotide (guanine to cytosine) substitution in 1 allele, resulting in an amino acid change in codon 717 (valine to leucine). This mutation is sufficient to cause early-onset Alzheimer disease in this family and supports further the amyloid hypothesis as the primary pathologic event in Alzheimer disease.
This Month in Archives of Neurology. Arch Neurol. 2000;57(6):781-782. doi:10.1001/archneur.57.6.781