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Pathologic Staging of Alzheimer Disease

Neuritic plaques (NP) and neurofibrillary tangles (NFT) are the two hallmark microscopic features of Alzheimer’s Disease (AD).  Several research groups have developed consensus approaches to evaluate the human brain for these characteristic changes of AD. Each of these approaches requires the neuropathologist to utilize specific methods to visualize these lesions using a microscope; these methods are commonly called "stains" because they were developed from the same chemistry used to produce dyes or stains for clothing. Common protocols to visualize NP and NFT with a microscope use stains that require silver or "silver stains."

The most commonly used criteria for evaluating AD are summarized below:

Braak and Braak Stage: This approach evaluates primarily the distribution of neurofibrillary tangles (NFT) within the brain. There are six stages, from I to VI. These criteria typically are used in the research setting.  While we list the usual clinical impression that corresponds to different Braak stages, it is important realize that there many exceptions.


NFT distribution

Typical Clinical Impression



Normal cognition



Cognitive impairment



Alzheimer disease

CERAD Score: This approach was proposed by the Consortium to establish a Registry for Alzheimer’s disease (CERAD) and evaluates the density of NP in specified regions of brain. The ranking includes sparse (A), intermediate (B), or frequent (C) NP density. The score for NP density is combined with clinical information for a final classification.

NIA-Reagan Institute Criteria: This approach combines the Braak and Braak Stage with CERAD Score to assign a probability that a patient’s dementia was caused by AD.

NIA-Reagan Institute Braak and Braak CERAD

Low Probability of AD

I or II A

Intermediate Probability of AD


High Probability of AD

V or VI


Again, it is important to realize that there are exceptions to this simplified view and other contributors to dementia also must be considered, such as stroke and Lewy body disease.

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