Alzheimer's Disease Education and Referral Center

100 years ago...

Diciembre 1, 2006
Dr. Alois Alzheimer

The year 2006 marked the 100th anniversary of Dr. Alois Alzheimer’s presentation of a case study of a 51-year-old German woman, Auguste D., who had been admitted to a hospital in 1901 with an unusual cluster of symptoms. Those symptoms included reduced comprehension and memory, aphasia, disorientation, unpredictable behavior, paranoia, auditory hallucinations, and pronounced psychosocial impairment. When Dr. Alzheimer first observed her in 1903, Auguste D. was bedridden, incontinent, and was becoming increasingly disoriented, delusional, and incoherent. She eventually required assistance to be fed, was unable to speak, and was often hostile. Hospital staff tried to keep her as safe and comfortable as possible, but little else could be done to treat her illness, and she died on April 8, 1906.

Dr. Alzheimer used the latest medical techniques and innovations, including a new silver tissue-staining method and greatly improved microscopes, to conduct the post mortem study of Auguste D.’s brain tissue. No stranger to the fields of pathology and psychiatry, Dr. Alzheimer was involved in a wide range of clinical studies of manic depression and schizophrenia. He worked at the Royal Psychiatric Clinic in Munich, Germany, for Dr. Emil Kraepelin, a leading psychiatrist. Dr. Kraepelin believed that most mental illnesses were actually organic brain diseases, as opposed to his rival, Dr. Sigmund Freud, who maintained that most mental illnesses were psychoses of the mind. Dr. Kraepelin’s Handbook of Psychiatry, was the first systematic classification of mental diseases.

The first “Alzheimer’s” case was presented at a meeting of the South-West German Society of Alienists (“alienists” were superintendents of early “insane asylums” and were usually psychiatrists) on November 3, 1906. Dr. Alzheimer’s paper, “Regarding a Curious Disease of the Cortex,” described numerous globs of sticky proteins in the spaces between neuron cells and “a tangled bundle of fibrils” within cells throughout the cortex.

These sticky proteins (plaques) and fibrils (tangles) had previously been seen only in the brains of much older patients diagnosed with “senile dementia.” At age 51, Auguste D. was thought to be far too young to be suffering from senile dementia, and Dr. Alzheimer’s “new” disease was initially classified as “presenile dementia.” Because of her age, clinicians did not consider the possibility that the plaques and tangles Dr. Alzheimer described could also be the cause of dementia in old age, thus the characterization as presenile dementia.

Dr. Alzheimer and his colleagues studied the histology of 5 cases with similar brain pathologies during the first decade of the new century. Although other researchers had linked the presence of plaques to symptoms of dementia seen in older people, it was Dr. Alzheimer who first observed both plaques and tangles in a younger patient.

Auguste D.-Patient of Dr. Alzheimer

It was not until 1910 that the term “Alzheimer’s disease” was coined by Dr. Kraepelin in his 8th edition of the Handbook of Psychiatry. He stated that “a particular group of cases with extremely serious cell alterations was described by Alzheimer…the plaques were excessively numerous and almost one-third of the cortical cells had died off. In their places, were peculiar, deeply stained bundles of neurofibrils.” He mentioned “Alzheimer’s disease” for the first time, stating, “The clinical interpretation of this Alzheimer’s disease is still unclear. Although the anatomical findings suggest that we are dealing with a particularly serious form of senile dementia, the fact is that this disease sometimes starts as early as in the late forties.”

In 1912, Dr. Alzheimer accepted an appointment as full professor of psychiatry at the University of Breslau (now Wroclaw, Poland), but his health deteriorated, and he was never able to fully carry out his university duties. From October 1915 onward, Alois Alzheimer became increasingly ill and finally died on December 19, 1915.

“In his day, Dr. Alzheimer’s discoveries were enormous strides forward. I believe that, just as Drs. Alzheimer and Kraepelin established the clinical pathways for researching this disease 100 years ago, we are creating strong foundations—in neuroimaging and genetics in particular—for the major discoveries to come,” commented Richard A. Hodes, M.D., Director, NIA. “Tremendous progress continues every day toward our efforts to conquer this disease.”

“Many of the world’s premier scientific thinkers are exploring every aspect of this highly complex disease. We’re discovering new information on AD’s earliest preclinical phases and intriguing insights into connections with other diseases and conditions,” said Marcelle Morrison-Bogorad, Ph.D., Director, Neuroscience and Neuropsychology of Aging Program, NIA. “New research is examining potential preventive mechanisms, molecular sequences, treatment, and caregiver interventions. Though pleased with our achievements, we’ll never be satisfied until we find a cure and ways to prevent the disease altogether.”

A Century of Research

1900s

  • Dr. Alois Alzheimer presents case study and Alzheimer’s disease is named.

1920s

  • Amyloid is identified as the core substance of plaques.

1930s

  • Familial AD is first suggested.

1940s

  • Belief persists that senile dementia is normal part of aging caused by cerebral arteriosclerosis.

1950s

  • Biological structure of plaques and tangles is investigated.

1960s

  • Landmark study suggests that dementia is directly related to the number of senile plaques present in the cerebral cortex.
  • Structure of neurofibrillary tangles is described as “paired helical filaments.”

1970s

  • National Institute on Aging is created and assumes lead role in AD research.
  • Mini-Mental State Exam is introduced.
  • Memory and cholinergic function are linked; reduction of choline acetyltransferase is seen in AD.
  • Editorial describes AD as a major public heath problem and “Alzheimer’s disease” becomes a common term.
  • Coalition of grass-roots AD advocacy groups begins to rally public awareness of and interest in AD research.

1980s

  • National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria are written.
  • Alzheimer’s Disease and Related Disorders Association forms, becomes the Alzheimer’s Association.
  • First Alzheimer’s Disease Research Centers are funded by NIA.
  • Diagnostic and Statistical Manual of Mental Disorders (DSM III) categorizes AD.
  • Clinical Dementia Rating (CDR) scale is established.
  • Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) is created by NIA.
  • AD is linked to chromosome 21 and amyloid precursor protein.
  • Beta-amyloid protein is sequenced.
  • NIA forms the Alzheimer’s Disease Education and Referral (ADEAR) Center.

1990s

  • FDA approves tacrine (Cognex) following successful clinical trial.
  • NIA funds Alzheimer’s Disease Cooperative Study.
  • First amyloid precursor protein (APP) mutation is discovered.
  • Early-onset genes and late-onset risk factor gene are discovered.
  • First in series of transgenic mice models is created.
  • Abnormal tau in neurofibrillary tangles is identified.
  • NIA-Reagan criteria for AD pathology diagnosis are developed.
  • Mutation in tau gene is cause of some chromosome 17 frontotemporal dementia.
  • National Alzheimer’s Coordinating Center is formed.
  • Mild Cognitive Impairment (MCI) characteristics are defined.

2000s

  • Clinical trials, initiatives, and studies examine cholinesterase inhibitors, anti-inflammatories, vitamins, statins, supplements, valproate, antioxidants, hormones, beta amyloid vaccines, and alternative medicines.
  • Late-onset Alzheimer’s Disease Genetics Study begins.
  • Alzheimer’s Disease Neuroimaging Initiative is launched.
  • Pittsburgh B compound is developed, allowing researchers to “see” amyloid plaques in PET scans.
  • Triple transgenic mouse is introduced.
  • New focus on translational studies to facilitate drug discovery and development begins.

 

Page last updated: Junio 26, 2013