Diagnosing Ad

At present there is no definitive method for pre-mortem diagnosis of AD. Accepted practice is for AD to be diagnosed postmortem by pathological examination of autopsy tissue. Histopathological analysis of post-mortem tissue uses criteria not appreciably different from those described by Alois Alzheimer himself in 1907 (10). The gross hallmarks are cortical atrophy, enlargement of the ventricles, and shrinkage of the hippocampus and surrounding areas of the medial temporal lobe.

Microscopic examination reveals diffuse neuronal death, and the presence of "senile plaques" and "neurofibrillary tangles." The plaques are a molecular admixture of amyloid peptides and other constituents, and they can be subdivided into two categories. Neuritic plaques contain a dense core of amyloid peptide aggregate and are surrounded by distressed neuronal processes. Diffuse plaques lack associated neuronal processes and exhibit a more diffuse deposition of amyloid. Plaques can be seen readily using silver stains or thioflavin stains—the advent of silver staining chemistry is, in fact, what allowed Alzheimer to make his landmark discovery (see figure).

Microscopy of post-mortem AD tissue also reveals the presence of neurofibrillary tangles in the cytoplasm of neurons in affected brain areas. Neurofibrillary tangles are insoluble deposits of hyperphospo-rylated tau protein (see text). An additional feature of AD is the presence of angiopathy, that is, pathology of the cerebral vascula-ture. Blood vessels in the AD patient exhibit amyloid deposition to varying degrees, an attribute that has been termed "hardening of the arteries."

Pre-mortem diagnosis of AD is an iffier proposition. Established criteria have been

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BOX 1 Microscopic features of Alzheimer's disease. (A) Several neuritic plaques within the cerebral cortex are seen on this silver stain. (B) Diffuse plaques predominate in this field of cerebral cortex. Silver stain. (C) Two neurofibrillary tangles are seen on silver stain. (D) A fluorescent stain (thioflavin S) reveals the ring-like profiles of amyloid within blood vessel walls in the meninges or coverings of the brain. The underlying cortical blood vessels also evidence amyloid angiopathy. Senile plaques in the cortex are also seen in this preparation. Reproduced from Khachaturian and Radebaugh (113).

BOX 1 Microscopic features of Alzheimer's disease. (A) Several neuritic plaques within the cerebral cortex are seen on this silver stain. (B) Diffuse plaques predominate in this field of cerebral cortex. Silver stain. (C) Two neurofibrillary tangles are seen on silver stain. (D) A fluorescent stain (thioflavin S) reveals the ring-like profiles of amyloid within blood vessel walls in the meninges or coverings of the brain. The underlying cortical blood vessels also evidence amyloid angiopathy. Senile plaques in the cortex are also seen in this preparation. Reproduced from Khachaturian and Radebaugh (113).

published under the aegis of the NIH (78) that when adhered to can give about 90% accuracy versus post-mortem assessment of the same individual.

Clinical diagnosis of AD requires the availability of a spouse or other frequent companion for cross-reference. Inaccurate recollection on the part of the patient themselves is a great confound, so that an informed acquaintance needs to be available to give an objective description

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