ArticlesDiagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease
Section snippets
Age-related vs. disease-related changes
IN recent decades the populations of developed industrial countries have experienced a marked increase in life expectancy. The distressing aspect of this change is the growing number of elderly people in clinically recognizable stages of slowly progressing illnesses 3, 22, 29, 30. Hence, it is important to distinguish disease-related lesions from morphologic changes inevitably developing with advancing age [16]. Regarding the brain, some age-related changes specifically develop only in humans.
Neuropathologic diagnosis of Alzheimer’s disease
A definite clinical diagnosis of Alzheimer’s disease (AD) cannot presently be made. Both false-positive and false-negative diagnoses occur in a significant proportion of cases, underscoring the necessity for neuropathologic confirmation of clinical assumptions [6]. Postmortem diagnosis of AD, by definition, requires proof of the presence of neurofibrillary tangles in the brain (cases of dementia without these changes must be classified as non-Alzheimer dementias). Brain changes found in cases
Brain-amyloid deposits
Amyloid protein deposits are abnormal structures that frequently, though not inevitably, occur in the brains of aged individuals. Simple amyloid deposits appear as patches and/or cored structures. Upon superficial examination, such cored structures can easily be mistaken for neuritic plaques. The term “senile plaque” is used variously for simple amyloid deposits, as well as for ill-defined amalgamations of simple amyloid deposits and neuritic plaques with dystrophic neurites containing
Neurofibrillary changes
Neurofibrillary changes of the Alzheimer type do not inevitably occur in the brain of aged individuals and thus must be considered abnormal. The distribution pattern and density of neurofibrillary tangles and neuropil threads roughly correspond to the clinical expression of AD 2, 3, 4, 5, 13, 17, 28.
The neurofibrillary changes developing in Down’s syndrome are virtually identical to those seen in AD. Elderly individuals suffering from Down’s syndrome are particularly prone to development of AD.
Evolution of the neurofibrillary changes
An early indicator of the brain destruction in AD is the subtle decline of memory functions. The clinical symptoms gradually worsen, eventually including impairment of somatomotor function. The progression of symptoms reflects the gradual development of AD-related brain changes. A particular weakness of the criteria presently in use in the neuropathological confirmation of AD is the allowance of only the distinction of fully developed cases of AD on the one hand and a broad spectrum of
Co-occurrence of other diseases
Very frequently, the brains of elderly demented patients are affected by more than one disease. A large proportion of mentally impaired Parkinson patients have concomitant AD-related pathology [15]. In addition, changes in brain vessels and specific lesions of non-Alzheimer dementias [8]often co-occur with Alzheimer-related pathology and complicate the pathological picture.
By applying the recommended advanced silver methods (the Gallyas technique for neurofibrillary changes and the
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