Prior to any evaluation of morphologic brain changes, a decision must be made whether a given alteration is associated with aging or with disease. Patients with disease-related lesions may be in a clinically silent phase of a disease or show overt symptoms. Neurofibrillary tangles and neuropil threads are the hallmarks of Alzheimer's disease. They should not be considered to be age-related changes, even when they are present only in small numbers. In general, the initial changes consist of neurofibrillary tangles and neuropil threads. Plaques (amyloid deposits and/or neuritic plaques) are consistently present in the end stage of the disease. Initial neurofibrillary tangles and neuropil threads develop at specific cortical predilection sites. The changes then spread in a predictable, nonrandom manner across other portions of the telencephalic cortex. The sequential changes in the distribution pattern of the lesions provide the basis for a staging procedure that takes the slow and gradual progression of the destructive process into consideration. The staging procedure provides accurate diagnoses in the initial stages and even reveals brain changes developing prior to the appearance of clinical symptoms. It is thus advantageous in characterizing nondemented controls. The staging procedure can be carried out easily and does not require knowledge of clinical data, quantitative assessments, or adjustments for the age of the patients. Application of advanced silver techniques (Gallyas, Campbell-Switzer) to demonstrate Alzheimer's disease-related lesions also allows recognition of the hallmarks of other disorders, such as Lewy body disease (Parkinson's disease) and dementia with argyrophilic grains, which frequently co-occur with Alzheimer's disease.