Page 358 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Alzheimer’s Disease
The occurrence of Alzheimer’s disease, the tration of the osmolyte inositol points to a dis-
most common cause of (senile) dementia order of cell volume regulation.
(about 70%), is favored by a genetic disposi- The death of neurons is accelerated by a lack
tion. However, the disease is not genetically of NGF or of NGF receptors and can be delayed
uniform. An especially severe form of the dis- by NGF.
Systems ease has an autosomal dominant inheritance. Meynert, in the hippocampus (especially CA1,
Cholinergic neurons in the basal nucleus of
Defects on chromosomes 1, 12, 14, 19, or 21
were found in families with Alzheimer’s dis-
the subiculum) and in the entorhinal cortex
(→ B1) are particularly affected by cell death,
ease. The defective gene on chromosome 19,
Neuromuscular and Sensory 4), the relevant gene on chromosome 21 for a such as the frontal lobes, anterior temporal
but neurons also die in other cerebral areas,
for example, codes for apolipoprotein E (ApoE
lobes, parietal lobes, olfactory cortex, hypo-
protein (β-amyloid precursor) that can be bro-
thalamus, locus ceruleus, and raphe nuclei.
ken down to small amyloid peptides. These
can on their own bunch themselves together
Neuronal death is accompanied by de-
into protein fibrils 7–10 nm long (→ A1).
creased formation and concentration of neuro-
transmitters in the brain. Acetylcholine is
These amyloid fibrils can then form aggre-
gates, 10 µm to several hundred µm in diame-
markedly affected: in the cerebral cortex and
crease in the concentration of choline-acetyl
in the brain of patients with Alzheimer’s dis-
transferase, the enzyme that is necessary for
ease (→ A2). In addition to extracellular amy-
10 ter (senile plaques), that are frequently found the hippocampus there is an up to 90% de-
the formation of acetylcholine. The concentra-
loid, these plaques contain distorted dendrites
and axons with abnormal intracellular neuro- tion of other neurotransmitters is also re-
fibrils. The formation of these atypical ele- duced, for example, norepinephrine, serotonin,
ments of the cytoskeleton apparently precedes somatotropin, neuropeptide Y, substance P,
the death of the neurons (see below). and corticotropin-releasing hormone ([CRH]
Certain mutations of the β-amyloid precur- corticoliberin).
sor gene promote the formation of senile A consequence of the degenerative changes
plaques. Amyloid deposits can also occur un- is an increased loss of cerebral functions
der the influence of other genetic or external (→ B2). The disease typically begins insidious-
factors. It is thought, for example, that toxins ly with subtle deficits of memory, neglect of
can penetrate the brain via the olfactory appearance and body hygiene, phases of con-
nerves and cause the disease. Amyloid depos- fusion, and taking wrong decisions. As the dis-
its also occur in trisomy 21 (Down’s syndrome) ease progresses, anterograde amnesia (→
that also leads to dementia. p. 346) will be followed by impairment of past
β-amyloid fibrils can react with receptors at memories as well as procedural memory. Le-
the cell surface, such as the receptor for ad- sions in the limbic system express themselves
vanced glycation end products (RAGE), and a alternately through restlessness and lethargy.
scavenger receptor (RA). Oxygen radicals Motor deficits (speech disorders, abnormal
formed as a result may increase the neuronal muscle tone, ataxia, hyperkinesia, myoclonus)
intracellular concentration of Ca 2+ (→ A3), occur relatively late.
possibly via depolarization of the cell mem- Creutzfeldt–Jakob disease, possibly caused
brane and activation of NMDA receptors. The by prions (proteinaceous infectious particles),
O 2 radicals and Ca 2+ promote cell death. In mi- is a neurodegenerative disease that, in addi-
croglial cells (→ A4) the activation of RAGE and tion to motor (e.g., ataxia) and psychogenic
RA stimulates the formation or release, respec- disorders, also leads to dementia.
tively, of NO, prostaglandins, excitotoxins, cy-
tokines, tumor necrosis factor (TNF-α), tumor
growth factor (TGF-β1), and fibroblast growth
348 factor (b-FGF). This results in inflammation
that also impairs neurons. Increased concen-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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