Scientists at the Max Planck Institute of Neurobiology,
Martinsried/Germany, and at the University of Munich have
rediscovered brain sections of the first case of
Alzheimer’s disease. A special report is soon to be
published in the journal Neurogenetics.
Alzheimer’s disease is the most common cause of dementia
in adult life and affects many million people worldwide. The
frequency of the disease is expected to increase rapidly
during the next decades due to the growing age of human
populations.
Alois Alzheimer first reported on the disease, which was
named after him by Emil Kraepelin in 1910, at the 37th
Meeting of the Southwest German Psychiatrists in Tübingen on
November 3, 1906. Alzheimer described a 51-year-old woman who
had come under his care in 1901 while he worked as an
attending physician in the Frankfurt Asylum. The original
case file of this patient, Auguste D., was discovered
recently, and it has been speculated that the patient’s
dementia was not caused by the typical neurodegeneration of
Alzheimer’s disease but by arteriosclerosis of the
brain. Unfortunately, the brain sections on which
Alzheimer’s original diagnosis was based remained lost
for decades.
A search for the tissue material of this first case of
Alzheimer’s disease was initiated in Munich because
Alzheimer had moved here in 1903 to join the Royal
Psychiatric Hospital. In his 1907 publication, Alzheimer
acknowledges his former boss, Prof. Sioli in Frankfurt, for
"letting him have for examination" the central
nervous system of Auguste D. Thus, it seemed likely that
Auguste D.’s brain was sent to Alzheimer in Munich after
the patient had died in Frankfurt on April 8, 1906. But where
to look precisely?
Alois Alzheimer actually published two papers on the disease
that now bears his name. Each of these papers contains
clinical as well as pathological data on a patient Alzheimer
had seen at the hospital. Alzheimer’s report on Auguste
D. is not a full-size research paper but an abstract
summarizing the presentation he gave in Tübingen. In
contrast, numerous figures, mainly drawings, which include
several examples of the histopathology of his first case were
published by Alzheimer in a large article in 1911 together
with a second case report. In the latter paper, Alzheimer
gives a detailed description of the clinical history and the
histopathology of a 56-year-old man, Johann F., who also
suffered from presenile dementia.
Led by the biographical data of Johann F. provided in
Alzheimer’s 1911 paper, an extensive search first turned
up histological sections of this second case (Neurogenetics
1997; 1: 73-80). Yet, it is the same collection of material
belonging to Alzheimer’s laboratory where the
histological slides from Auguste D.’s brain have now
been found. Examination of these tissue sections showed a
large number of neurofibrillary tangles and amyloid plaques
in the cerebral cortex of Alzheimer’s patient
("neurofibrillary tangles" represent changes in the
cytoskeleton of nerve cells which are often associated with
cell death, and "amyloid plaques" are extracellular
deposits of a probably neurotoxic substance). Thus, taking
the clinical picture of Auguste D. into account, Alois
Alzheimer's first case represents a typical example of
Alzheimer’s disease also according to today's standards.
Genotyping for the apolipoprotein E epsilon 4 allele revealed
absence of this Alzheimer disease "risk factor" but
at the same time demonstrated that mutation analysis of the
more than 90 year old brain tissue is still feasible.
A comparison of the neuropathology of Auguste D. with that of
Alois Alzheimer’s second published patient, Johann F.,
is interesting since it represents an early illustration of
the spectrum of Alzheimer’s disease as we understand it
today. The special importance of the case of Auguste D. lies
in the fact that it marks the beginning of Alzheimer disease
research and that the neurofibrillary tangles, which now
represent an important topic of neuroscience research in
their own right, were first described in her brain.
Journal
Neurogenetics