I believe the statement " but AD cases have been reported with no tangles or with few plaques" is a scientific blunder and should be removed.

On the one hand, not all dementia cases are due to Alzheimer disease (AD). On the other, tangles or plaques are found in aging (which one could call "infra-AD").

Statistically, you can find non-Alzheimer dementia, with the load of lesions due to aging/infra-AD. If the nature of dementia is not known in those cases, which happens sometimes, you can say that you are dealing with AD with unusual levels of lesions. But you are simply wrong in stating that AD can occur without tangles or with few plaques, unless you demonstrate that clearly.

View all comments by Andre Delacourte

Most of the primary literature and latest textbooks reveal that amyloid beta plaques and tangles are most often associated with AD, and that most other pathologies of the brain that are absent of the aforementioned proteins can be either determined or that AD can be relatively safely ruled out. AD has become a disease of too many "subtypes." If we are going to classify many different, pathological presentations as AD, we had better deliver more compelling evidence from research to not only help ourselves, but inform the public with greater accuracy.

View all comments by Jacob Mack

This issue can't be resolved without getting lost in semantics. The clinical diagnosis of Alzheimer disease is based on consensus (NINCDS-ADRDA). Therefore, the statement that "cases of AD have been reported with no tangles and few plaques" translates into: there have been case-reports of patients who, in live, fulfilled clinical criteria for AD, but who, on autopsy, had few plaques or no tangles." We can simply conclude that these patients are false-positive inclusions of the diagnostic test criteria.

The discussion should be split in two:
1. Consider all subjects with plaques and tangles. Then, let's argue why the clinical presentation differs that much (i.e., some are considered " normal", others have different AD severity)
2. Consider that all dementias have clinical overlap. Occasionally, patients with vascular dementia, FTD, Lewy body dementia/PDD will end up meeting the NINCDS_ADRDA criteria for AD.

View all comments by Jurgen Claassen