Vol 5 n° 1 - Dementia
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ver the past 2 decades, the diagnostic classifica- tion of dementias has been continuously adapted to the increasing knowledge derived from clinical symptomatol- ogy, neuropathology, biochemistry, and clinicopathological comparisons. Before, dementias were attributed primarily to cerebral vascular insufficiency. Later, with the diagno- sis of Alzheimer’s disease (AD) predominating, further differentiations were categorized: frontotemporal demen- tia (FTD), dementia with Lewy bodies (DLB), vascular dementia (VD), prion disease, dementia with argyrophilic grains, British dementia, and many more. This develop- ment was driven by the results of molecular analyses of the abnormal protein deposits in the brain of the respective diseases in relation to the clinical syndromes.The careful clinical and neurochemical investigation of dementias has led to practical guidelines and improvements in current treatment and care, eg, the use of atypical neuroleptics in patients with DLB due to the high susceptibility to side effects by treatment with typical antipsychotics. More excitingly, the dissection of the molecular mecha- nisms and species involved in the aggregation process may allow for the development of specific therapies, which may, in the future, contribute to the prevention and treatment of neurodegenerative diseases. The following diseases are characterized by the deposition of protein aggregates, termed amyloid, derived from the Greek amylum (starch, sugar); the term was first intro- duced by Virchow in 1854 on the basis of color after stain- ing with iodine, since he assumed that polysaccharides were the major constituents of amyloid deposits in periph- eral tissues.1 The secondary structure of amyloid deposits both in the brain as well as in peripheral organs shows a strong tendency towards formation of b-pleated sheets; the tertiary structure forms high-order quasi-crystalline com- plexes that are birefringent under polarized light (eg, when stained with Congo red), and fibrils can be identified by electron microscopy.1,2 Table I lists the neurodegenerative diseases associated with deposition of abnormal proteins in the brain. B a s i c   r e s e a r c h 2 7 Biochemical aspects of dementias Christoph Hock, MD O Keywords: dementia; -amyloid; prion disease; tauopathy; -synuclein Author  affiliations:  Division  of  Psychiatry  Research,  University  of  Zurich, Zurich, Switzerland Address  for  correspondence:  Division  of  Psychiatry  Research,  Psychiatry University Hospital, University of Zurich, Lenggstrasse 31, PO Box 68, CH- 8029 Zurich, Switzerland
(e-mail: chock@bli.unizh.ch ) Alzheimer’s disease, frontotemporal dementia, dementia with Lewy bodies, and prion diseases are age-related neuro- degenerative  disorders  associated  with  a  progressive decline of cognitive brain functions. Due to the increase in prevalence rates, and the rising costs associated with clinical and social care, treatments designed to prevent or reverse these diseases are urgently needed. The most com- mon major biochemical characteristic of these neurode- generative diseases is the deposition of abnormal protein aggregates in brain. The decryption of the mechanisms of aggregation and associated neurotoxicity may reveal new therapeutic targets, which will enable treatment for these devastating conditions.   Dialogues Clin Neurosci. 2003;5:27-33.