Selective Cell Death of Hyperploid Neurons in Alzheimer’s Disease

• Published in: The American journal of pathology Vol. 177; no. 1; pp. 15 - 20
• Main Authors: Arendt, Thomas, Brückner, Martina K, Mosch, Birgit, Lösche, Andreas
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.07.2010; American Society for Investigative Pathology
• Subjects: Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Animals; Biological and medical sciences; Brain - cytology; Brain - pathology; Brain - physiology; Cell Death - genetics; Cell Differentiation - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Neurology; Neurons - cytology; Neurons - pathology; Neurons - physiology; Organic mental disorders. Neuropsychology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polyploidy; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Short Communication; Nervous system diseases; Anatomic pathology; Neuron; Alzheimer disease; Cell death; Central nervous system disease; Degenerative disease; Cerebral disorder; Apoptosis
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2010.090955

Aneuploidy, an abnormal number of copies of a genomic region, might be a significant source for neuronal complexity, intercellular diversity, and evolution. Genomic instability associated with aneuploidy, however, can also lead to developmental abnormalities and decreased cellular fitness. Here we show that neurons with a more-than-diploid content of DNA are increased in preclinical stages of Alzheimer’s disease (AD) and are selectively affected by cell death during progression of the disease. Present findings show that neuronal hyperploidy in AD is associated with a decreased viability. Hyperploidy of neurons thus represents a direct molecular signature of cells prone to death in AD and indicates that a failure of neuronal differentiation is a critical pathogenetic event in AD.