Brain shrinkage means dementia

Alzheimer's brain changes

Neuropathological basics

The diagnosis of "Alzheimer's dementia" can only be confirmed after death by means of a histological examination of the brain. A brain biopsy on the patient is risky and for ethical reasons only permitted in exceptional cases because neurologists and psychiatrists are now able to recognize the clinical picture and make the diagnosis with a very high degree of reliability, including completely painless additional tests.

The morphological criteria of Alzheimer's dementia are cytoskeletal changes (neuritic plaques, neurofibrillary degeneration) with the formation of double helix-like filaments from abnormally hyperphosphorylated, microtubule-associated tau protein triplets and the detection of ß-amyloid deposits (Aß) outside the nerve cells in the form of senile ones Plaques and in the blood vessels (see picture of tissue changes, Alzheimer's plaque, Taupathology and amyloid angiopathy). Because of the loss of nerve cells as a result of progressive damage to the neuronal cytoskeleton, the brain shrinks (see images of the brain laterally normal and brain atrophy). The connection between Aß deposition and tau pathology, synapses and cell loss has not yet been clarified.

Neurochemical basics

The cortex is innervated by four neuron systems, which are characterized by different neurotransmitters (acetylcholine, serotonin, noradrenaline and dopamine). In the brains of patients with AD, the cholinergic system is most severely affected and the earliest, and these have a 30-75% lower acetylcholine content than healthy people. The key role of the neurotransmitter acetylcholine in connection with learning and memory processes has been established. The rate of acetylcholine synthesis correlates with the level of cognitive skills.

Based on this cholinergic hypothesis, cholinergic substitution therapies have been developed with the aim of improving impaired cholinergic neurotransmission. Of the three possible therapeutic approaches (presynaptic, synaptic and postsynaptic), the inhibition of acetylcholinesterase (a protein that breaks down acetycholine) has proven to be clinically effective. By blocking the acetylcholinesterase and thus the acetylcholine breakdown in the synaptic gap, the remaining acetylcholine is longer effective at the postsynaptic receptors.

Tissue changes: Alzheimer's plaques, taupathology and amyloid angiopathy
(Courtesy: Kurt Jellinger, ICN, Vienna)

Brain laterally normal
(Courtesy: Kurt Jellinger, ICN, Vienna)

Brain atrophy in Alzheimer's disease
(Courtesy: Kurt Jellinger, ICN, Vienna)