Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis

Abstract

In 1911, Alois Alzheimer published a detailed report (Zbl. ges. Neurol. Psych. 4: 356-385) on a peculiar case of the disease that had been named after him by Emil Kraepelin in 1910. Alzheimer describes a 56-year-old male patient (Johann F.) who suffered from presenile dementia and who was hospitalized in Kraepelin's clinic for more than 3 years. Post-mortem examination of the patient's brain revealed numerous amyloid plaques but no neurofibrillary tangles in the cerebral cortex, corresponding to a less common form of Alzheimer disease which may be referred to as 'plaque only'. We have identified well-preserved histological sections of this case and performed mutational screening of exon 17 of the amyloid precursor protein gene and genotyping for apolipoprotein E alleles. The patient was shown to be homozygous for apolipoprotein allele epsilon3 and lacked APP mutations at codons 692, 693, 713 and 717. This case is of historical importance as it may have convinced Kraepelin to name the disease after his co-worker, Alois Alzheimer.

A critical analysis of the ‘amyloid cascade hypothesis’

“…Alzheimer's disease was first recognised as a distinct disease entity in 1910 and was named after Alzheimer by Kraepelin based on the clinical and pathological description of the original cases [52]. Of the two original cases described by Alzheimer [2], however, both had numerous SP but only one of the cases had significant numbers of NFT [52], thus creating a controversy as to the relationship between the two 'signature' pathological features [58,72,87]. In addition, SP and NFT can develop alone in different disorders, e.g., NFT in tangle-only dementia [143] and Aβ in hereditary cerebral haemorrhage with amyloidosis of the Dutch type (HCHA-D) [64].…”

Alzheimer's Disease: Approaches to Pathogenesis in the Genomic Age

“…Interestingly Alzheimer described Auguste D as having both the pathologies that we now know as plaques and tangles in her cerebral cortex but Johan F as having only plaques. Graeber and colleagues re-examined Alzheimer's original sections 90 years later and confirmed the original histopathological findings for Johann F (Graeber et al, 1997) and Auguste D (Graeber et al, 1998). In accordance with Kraepelin's original classification the term Alzheimer's disease or Alzheimer's presenile dementia continued to be exclusively used for a rare disease of mid-life until the 1970's when neuropathologists realised that the more common senile dementia and the type described by Alzheimer were indistinguishable (Terry and Katzman, 1983).…”

On the ‘classification’ of neurodegenerative disorders: discrete entities, overlap or continuum?

“…Hence, the original clinico-pathological description of AD originated in Alzheimer's detailed report of 1907 [1] of a case of presenile dementia associated with the presence of numerous senile plaques (SP) and neurofibrillary tangles (NFT) [59,60]. Similarly, the description of PiD was based on a series of patients characterised by cognitive disturbance, personality change and focal symptoms [116] and DLB on the description of patients by Lewy with 'paralysis agitans' accompanied by the formation of SP and NFT [45,87].…”

“…The second of the two original cases of 'AD' described by Alzheimer was characterised by numerous SP but lacked NFT [59]. Hence, even in the earliest des cribed cases of AD there was pathological heterogeneity raising the question as to whether 'plaque-only' cases should be regarded as AD [99].…”

“…The traditional method of classifying neurodegenerative diseases is based on the original clinicopathological concept, viz., a disease entity is a specific combination of clinical features and a distinctive neuropathology [40,45,59]. It was this principle, originally applied to small numbers of cases, that resulted in the first descriptions of Alzheimer's disease (AD) [1,60], Pick's disease (PiD) [116], dementia with Lewy bodies (DLB) [45,87], Creutzfeldt-Jakob disease (CJD) [32,75], and progressive supranuclear palsy (PSP) [128].…”