A possible pathogenesis for Alzheimer's disease: craniomaxillofacial dysfunction leading to localized cerebrospinal fluid stasis.
In the last two decades, a voluminous amount of research from multiple disciplines has been generated for Alzheimer's disease (AD). Despite the increased knowledge and understanding of AD and the potential therapeutics that are emerging, there is still no clear understanding of the pathogenesis. Without a precise, known mechanism, current potential targets for treatment may fall short of addressing an underlying cause. Any hypothesis must not only account for pathologic findings, but also the neurologic findings. Proposed hypotheses in the past have not completely accomplished this task, and have left many research findings unexplained. As AD is considered a heterogeneous disease, it may be helpful to compare and contrast it to other heterogeneous medical conditions. It is possible that today, there is sufficient knowledge and research on AD, but insufficient integration of that information. Thus, a unifying hypothesis that attempts to integrate much of the interdisciplinary research is presented to explain AD under a new paradigm. Stasis of cerebrospinal fluid (CSF) has been previously suggested to be a factor in the etiology of AD, but it has generated little attention among researchers. Therefore, CSF is discussed in greater detail and how disruption of its flow may have adverse consequences. The following hypothesis proposes that dependent, localized cerebrospinal fluid stasis in select areas of the brain may be one way to initiate and perpetuate AD pathogenesis. In that vein, it is also proposed that craniomaxillofacial function, involving the dentition and paranasal sinuses, plays a vital role for proper CSF flow dynamics. In this way, a possible mechanical risk factor involving a compromised craniomaxillofacial complex will be described for AD. The identification of a mechanical risk factor would open a discussion for immediate, inexpensive possibilities to prevent AD.
Lee
Susan J
SJ
Southern California Center for Facial Surgery, Tarzana, CA 91356, USA. slee1673@hotmail.com
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000503:physiopathology; D001921:Brain / Q000033:anatomy & histology* / Q000098:blood supply; D015170:Cerebrospinal Fluid Pressure / Q000502:physiology*; D003392:Cranial Sinuses / Q000033:anatomy & histology*; D006801:Humans; D008446:Maxillofacial Injuries / Q000150:complications*; D012307:Risk Factors