Alzheimer disease (AD) is defined as “an irreversible, progressive brain disorder that slowly destroys memory and thinking skills” (National Institute on Aging) and is pathologically characterized by abnormal deposition of neurofibrillary tangles and amyloid plaques. However, these abnormal protein aggregates also accumulate with aging, which complicates the distinction between aging and AD.

This presentation will discuss the concepts of disease and then compare and contrast these with the definition of Alzheimer disease. It briefly discusses causality and examines how associations have to be conflated with causality in the pathological diagnoses of neurodegenerative diseases. It also indicates some inherent biases that pathologists have in identifying disease and the pathological changes resulting from diseases. The presentation will present examples from the Calgary Brain Bank of patients without known neurodegenerative disease who die at different ages, as well as different pathological presentations of neurofibrillary tangles and amyloid plaques. Several known causes of AD will be reviewed and contrasted with what is commonly considered “normal aging”.

This presentation argues that Alzheimer disease pathology represents a final common pattern of changes that results from several or possibly many different aetiologies. Recognizing that these changes have several different causes might better guide future research into late onset dementias.

This presentation will enable the learner to:

1. 1. Consider observational biases used in the diagnoses of different dementias

2. 2. Distinguish several aetiologies of Alzheimer-type Neuropathology

3. 3. Contemplate how neuropathology has done a disservice in dementia research by focusing on accumulations of abnormal proteins