Experienced neuropathologists recognize a form of Alzheimer disease, particularly in older patients (beyond 75 years of age), in which there are senile plaques but few or no neuronal tangles (about 20 percent of 150 cases reported by Joachim et al). Increasingly, other pathologic changes are being appreciated in Alzheimer cases with fewer plaques and tangles than anticipated for the degree of dementia; Lewy bodies in particular are found by sophisticated techniques. Another problem for the neuropathologist is to distinguish between the normal-aged brain and that of Alzheimer disease. This accords with the difficulty in understanding the role of aging in this disease, as mentioned earlier. It is not unusual to find a scattering of senile plaques in individuals who were ostensibly mentally normal during life. Anderson and Hubbard studied 27 demented individuals aged 64 to 92 years and 20 age-matched nondemented controls. In the former, 3 to 38 percent of the hippocampal neurons contained neurofibrillary tangles; in all but 2 of the controls, the number of hippocampal neurons with tangles fell below 2.5 percent. Moreover, an increased number of tangles in the aged are associated with mild cognitive impairment and a higher likelihood of progression to Alzheimer disease.
Many demented individuals with clinical features of Alzheimer disease have sufficient neuronal loss and Lewy bodies in the cortex and substantia nigra to justify a diagnosis on histopathologic grounds of Parkinson disease (see further on). For example, Leverenz and Sumi found that 25 percent of their Alzheimer patients showed the pathologic (and clinical) changes of Parkinson disease, a much higher incidence than can be attributed to chance. Similarly, of 11 patients with progressive supranuclear palsy (also discussed further on) reported by Gearing and coworkers, 10 were demented and 5 had the neuropathologic features of Alzheimer disease. These mixed cases present problems not only of classification but also in understanding the neurobiology of these degenerative diseases. This subject is discussed further in the section on Parkinson disease.
It is of historical interest that Alzheimer was not the first to describe plaques, one of the hallmarks of the pathologic state. Miliary lesions (Herdchen) had been observed in senile brains by Blocq and Marinesco in 1892 and were named senile plaques by Simchowicz in 1910. In 1907, Alzheimer described the case of a 51-year-old woman who died after a 5-year illness characterized by progressive dementia. Throughout the cerebral cortex he found the characteristic plaques, but he also noted, thanks to the use of Bielschowsky’s newly devised silver impregnation method, a clumping and distortion of fibrils in the neuronal cytoplasm, the neurofibrillary change (tangles) that now, appropriately, carries Alzheimer’s name.