2015-07-25

Back to the future: Alois Alzheimer's and Gaetano Perusini's initial reports

Even though nowadays AD is almost always described as dementia caused by progressive neurodegeneration that is characterized by two neuropathological hallmarks (amyloid plaques and neurofibrillary tangles, regarded by many as causative agents), this hasn't always been the case.

Courtesy of Alzheimer's Disease Research, a program of the BrightFocus Foundation.

Indeed, the neuropathologists that first described this disease at the turn of the last century, Alois Alzheimer and Gaetano Perusini, also reported two other prominent neuropathological features of AD, lipidosis and gliosis. Unfortunately, for the longest time, these two additional hallmarks have been either completely forgotten (lipidosis) or merely considered reactive changes (gliosis). It is kind of sad that it took 100 years and all the money, technology and scientific effort required to develop the capability of performing genome-wide association studies, to (re)discover that lipid/cholesterol metabolism and innate immune cell function are likely critical players in the etiology of AD [PMID:21085570].

In his famous one-case report of 1906/1911, Alois Alzheimer described the now homonymous disease as characterized by:
  • “minute miliary foci caused by deposition of a particular substance in the cortex” [amyloid plaques]
  • “quite striking changes of the neurofibrils” [neurofibrillary tangles]
  • “extraordinarily strong accumulation of lipoid material in the ganglion cells, glia and vascular wall cells” [lipidosis]
  • “particularly numerous fibril-forming glia cells” [gliosis]

and Gaetano Perusini shortly after (1909/1910) reported that the far more numerous cases he analyzed where “characterized anatomically by atrophy of the cerebral cortex of the most extreme degree, whereby massive cellular loss, a peculiar fibrillary disorder of the ganglion cells, strong proliferation of the fibril-producing glia, deposition of unusual metabolic products in the form of plaques in the cerebral cortex, moderate proliferative phenomena of the vasculature, and major accumulation of lipoid products in the ganglion cells, glia and vasculature occur.”

It is important to note that, at the time, neurons were referred to as "ganglion cells".

For a more thorough and extended historical account on the topic, the interested reader should refer to the nice review by Dr Paul Foley titled "Lipids in Alzheimer's disease: A century-old story" [PMID:20471492].

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