Neural Transplantation in Dementia
As other chapters in this volume attest, the intracerebral grafting (ICG) of neural tissue is now well established as an effective strategy for anatomic reconstruction and functional repair in a variety of neural systems in the brain. Moreover, preliminary trials have commenced of the clinical applications of the ICG paradigm to a number of neurodegenerative diseases, most notably parkinsonism (see chapter by Brundin and Lindvall, this volume). One of the fundamental conditions for the development of a rational ICG therapy is the identification of the target population(s) of cells central to the disease process, which one consequently seeks to replace. The failure as yet to identify the primary basis of the disease process in human dementia not only represents the biggest problem for developing an effective ICG strategy for the disease but restricts even the determination of the fundamental issue whether such a strategy might be feasible.
KeywordsNerve Growth Factor Cholinergic Neuron Basal Forebrain Radial Maze Hirano Body
Common Terminology in Research on Alzheimer’s Disease
- Senile dementia
A class of diseases of old age, leading to progressive functional deterioration of cognition, attention, learning, and memory.
- Alzheimer’s disease (AD)
A neurodegenerative disease that is the commonest cause of dementia. Its diagnosis is based on the presence post mortem of specific neuropathologic hallmarks: neurofibrillary tangles and senile plaques in the neocortex and hippocampus.
- Senile dementia of the Alzheimer type (SDAT)
Because a final diagnosis of Alzheimer’s disease can only be made post mortem, patients whose dementia is characteristic of AD should in life strictly be diagnosed as having SDAT.
- Neurofibrillary tangles (NFTs)
Dense accumulations of fibrous deposits within the cytoplasm of neurons, usually visualized in silver-stained brain sections. In AD, they are predominant in large pyramidal neurons of the neocortex and hippocampus.
- Paired helical filaments (PHFs)
Electron-microscopic studies have shown that the NFTs of AD are made up of fine filaments that are twisted together to form regular paired helical structures.
- Tau protein
The major protein constituent of the PHFs. It has recently been sequenced and is found to occur in 6 isoforms in the brain.
- Senile (or neuritic) plaques
Extracellular tangles of neurites with a core of amyloid. Plaque deposits in the cortex and hippocampus are a second diagnostic neuropathologic feature of AD.
Amyloid is an extracellular deposit in many tissues that is defined by its particular optical properties when viewed under polarized light.
- β/A4 amyloid protein
The particular form of amyloid that is deposited in extracellular spaces and around blood vessels in AD:It has been sequenced and is found to consist of a 42 amino acid protein. It is thought to be an abnormal cleavage product of the precursor protein APP.
- Amyloid precursor protein (APP)
Cloning of the β/A4 protein has enabled the sequencing of the full APP precursor protein. There are 3 isoforms in the brain, 695,751, and 770 amino acids long. APP is believed to be a membrane-bound protein, with the β/A4 protein located close to its C-terminal end in the region thought to span the membrane. The function of APP in the intact CNS is at present unknown.
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