Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- 27 Mild cognitive impairment
- 28 Alzheimer's disease: overview
- 29 The neuropathology of Alzheimer's disease in the year 2005
- 30 Genetics of Alzheimer's disease
- 31 The role of ß-amyloid in Alzheimer's disease
- 32 Treatment of Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
30 - Genetics of Alzheimer's disease
from Part IV - Alzheimer's disease
Published online by Cambridge University Press: 04 August 2010
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- 27 Mild cognitive impairment
- 28 Alzheimer's disease: overview
- 29 The neuropathology of Alzheimer's disease in the year 2005
- 30 Genetics of Alzheimer's disease
- 31 The role of ß-amyloid in Alzheimer's disease
- 32 Treatment of Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
Summary
Introduction
Alzheimer's disease, the most common form of age-related dementia, is characterized by progressive and insidious neurodegeneration of the central nervous system eventually leading to a gradual decline of cognitive function and dementia. The key neuropathological features of AD are abundant amounts of neurofibrillary tangles and β-amyloid (Aβ) deposited in the form of senile plaques. Although the knowledge of disease pathophysiology still remains fragmentary, it is now widely accepted that, similar to other common diseases like diabetes, coronary artery disease, or breast cancer, genes play an essential role in predisposing to onset and/or in modifying the progress of the disease.
Genetically, AD is a complex and heterogeneous disorder: it is complex because there is no single mode of inheritance that accounts for its heritability. Moreover, disease inheritance shows an age-related dichotomy in which rare but highly penetrant mutations transmitted in an autosomal dominant manner are almost exclusively responsible for the early-onset familial forms of AD (EOFAD), while common polymorphisms with low penetrance appear to have their greatest effect on the more frequent late-onset form of the disease (LOAD; Tanzi, 1999). It is heterogeneous because genetic variants in multiple genes on several chromosomes throughout the genome are involved together with non-genetic factors. All of the known factors contribute to the increased accumulation of Aβ (more specifically: Aβ42) owing to an imbalance in production vs degradation/clearance in the cell (Fig. 30.1, 30.2).
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- Chapter
- Information
- Neurodegenerative DiseasesNeurobiology, Pathogenesis and Therapeutics, pp. 441 - 451Publisher: Cambridge University PressPrint publication year: 2005