Early Alzheimer's disease genetics.
ABSTRACT The genetics community working on Alzheimer's disease and related dementias has made remarkable progress in the past 20 years. The cumulative efforts by multiple groups have lead to the identification of three autosomal dominant genes for early onset AD. These are the amyloid-beta protein precursor gene (APP), and the genes encoding presenilin1 and 2. The knowledge derived from this work has firmly established Abeta as a critical disease molecule and lead to candidate drugs currently in treatment trials. Work on a related disease, frontotemporal dementia with parkinsonism - chromosome 17 type has also added to our understanding of pathogenesis by revealing that tau, the protein component of neurofibrillary tangles, is also a critical molecule in neurodegeneration. Lessons learned that still influence work on human genetics include the need to recognize and deal with genetic heterogeneity, a feature common to many genetic disorders. Genetic heterogeneity, if recognized, can be source of information. Another critical lesson is that clinical, molecular, and statistical scientists need to work closely on disease projects to succeed in solving the complex problems of common genetic disorders.
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ABSTRACT: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2011; 7(3):270-9. · 14.48 Impact Factor
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ABSTRACT: Neðst á síðunni er hægt að nálgast ritgerðina í heild sinni með því að smella á hlekkinn View/Open Previous studies on first-degree relatives of Alzheimer’s disease (AD) patients have revealed a higher risk of developing dementia, and that subtle cognitive impairment can be detected before overt clinical signs appear using neuropsychological tests. Findings on children of AD patients are very scarce within the literature. The main aim of this study was to explore the cognitive development of adult children (AC) of AD patients in Icelandic pedigrees selected from an ongoing genetic research, over a seven-year period. The subjects were 83 AC (age range 46-74) with a family history of AD and a control group (NC) constituting 30 individuals (age range 48-73) without any known first-degree relative with dementia. Cognitive abilities were assessed using neuropsychological tests of orientation, verbal and non-verbal memory, abstract reasoning, language, concentration, mental speed, and visuo-spatial and constructional abilities. Participants with known central or peripheral nervous disorders were excluded from the study. Primary results revealed no statistical difference between the two groups on any of the neuropsychological tests from time 1 to time 2, over a seven year period. These findings place the onset of subtle cognitive impairments in adult children of AD patients after the age of 60 years. When comparing the AC group to 76 AD patients and 92 siblings of AD patients, participating in the genetic study, one AC had stronger resemblance to the AD group than other AC on the neuropsychological measures. Furthermore, 10% of the AC group had stronger resemblance to the siblings of AD patient in the neuropsychological measures than the rest of the group, indicating a possible trend within the AC group.
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ABSTRACT: Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.The Journals of Gerontology Series A Biological Sciences and Medical Sciences 12/2010; 65(12):1269-74. · 4.31 Impact Factor