Recent preprint by Jeff Kordower et al. suggests tau (not alpha-syn) is the initial pathology in nigrostriatal dopamine neuron degeneration

[jeffreyn]

"These data should change our thinking of PD pathology and therapies directed towards reducing pathological tau might be a better strategy than those directed at α-syn."

Research paper preprint (not yet peer-reviewed):

Is Tau the Initial Pathology in Dopaminergic Nigrostriatal Degeneration? Studies in Parkinsonism and Parkinson’s Disease.

biorxiv.org/content/10.1101...

[park_bear]

We have mouse models that produce defective human Alpha synuclein and develop Parkinson's symptoms. The patients in this study did not actually have a Parkinson's diagnosis. Of course, defective tau protein may also produce problems.

[jeffreyn in reply to park_bear]

61 patients examined, 61 brains examined post mortem (Religious Orders Study)

24 had sporadic PD (22 with tau pathology)

28 had mild motor deficits (all with tau pathology, 17 with Lewy pathology also)

9 had no symptoms (and no tau or Lewy pathology)

As they say, it is striking that 22/24 PD cases, and 28/28 MMD cases, had tau pathology. In contrast, they say elsewhere that in some studies, 50% of PD brains have tau inclusions.

Given all that, and the relatively small sample size, the quote I included in my initial post seems a bit strong. Perhaps they could have just said that more effort should now be put into researching the role of tau pathology in Parkinson's Disease.

[jeffreyn in reply to jeffreyn]

After spending more time on this paper, I have changed my mind. The quoted statement deserves to be strong, because the evidence is strong.

I look forward to seeing what the PD research community thinks, after peer review and publishing have been completed.

[MarionP in reply to jeffreyn]

Religious Orders Study can you give me a reference for this religious order study, just the three words alone may not be enough as a search term it may generate way too many leads cuz it's a little general.

I would appreciate it very much thanks... Perfect timing because in a little over a week I'm seeing my neurologist and since he is also a researcher or at least he has a research degree to go with his MD I wanted to be able to talk to him about both of these studies and have him look at them, at least be able to hand him the references and he can look at the abstracts right away and who knows maybe he's even able to get into the study text of the religious orders study, and then maybe get a spontaneous comment and then a bit later after he's read them both through then I expect he would have more to say, which I'd also be happy to share if anybody cares...also I plan to show him Park bears comment it sure looks relevant to me too.

And I even have a way to get him to open up a little... Having to do with the idea of I don't plan on letting him wait for the definitive gold study result of postmortem examination, so I plan to pester him until he says something to me while I'm still on this side of the ground.

[jeffreyn in reply to MarionP]

I searched the PDF file for "Religious Orders Study". It is only mentioned once (without reference), in a section called "Subjects" (reproduced below).

"Subjects

We analyzed brain tissues from older adults with no motor deficit (NMD; n=9), with mild motor deficits (n=28), and with sporadic PD (n=24). Subjects with mild motor deficits were further categorized based on the presence (MMD-LB, n=17) or absence (MMD, n=11) of nigral Lewy pathology (Table 1). Each subject signed an informed consent for clinical assessment prior to death and an anatomic gift act for donation of brain at the time of death. These subjects with NMD, MMD, and MMD-LB were participants in the Religious Orders Study, a community-based cohort study of chronic conditions of aging who agreed to brain autopsy at the time of death and were examined by a neurologist or geriatrician at the Rush Alzheimer’s Disease Center. All adults with sporadic PD were diagnosed by movement disorder specialists in the department of Neurological Sciences at Rush University Medical Center. All cases were evaluated pathologically by a board-certified neuropathologist who confirmed that these subjects did not have pathologies that met a diagnostic criteria for any other neurodegenerative disease. The Human Investigation Committee at Rush University Medical Center approved this study."

[jeffreyn]

Hi Chelo,

Your reply to Shirlzoni somehow ended up in my thread. I'm sorry I took so long to spot it and get back to you.

Jeff

[HekateMoon in reply to jeffreyn]

Whoops! Ill delete. Sorry.