Thread by @relajoie

🚨🧠📄🍾 🤪🥳 For some reason all our papers are coming our within 2 weeks!
Here’s the latest in @GreenJournal, on the relationships between 1) patterns #tau and #amyloid PET and 2) #Alzheimer’s clinical #heterogeneity and #APOE4.

n.neurology.org/content/early/…

1/n

#Alzheimer is associated with #heterogeneous clinical presentations. Patients develop symptoms at different ages (even sporadic AD can start early) and clinical syndromes vary: not everyone shows a “typical” amnestic syndrome (which is not very sensitive nor specific to AD!)

2/n

Specific non-amnestic syndromes are often associated with AD, like #PosteriorCorticalAtrophy (PCA, the visual variant of AD) or the logopenic variant of Primary Progressive Aphasia (lvPPA).

#APOE4 is associated with an earlier onset but also a more amnestic syndrome.

3/n

Here, we wanted to see how these three factors (clinical syndrome, age of onset, and APOE4) relate to brain pathology measured with #PET in living patients. We studied 119 consecutive patients from @UCSFmac. All had MCI or dementia and were amyloid-positive.

4/n

Looking at global cortical signal, we saw no association btw amyloid-PET and age at PET, disease severity, or syndrome.
In contrast, tau-PET was independently associated with all measures (higher tau ↔️ younger age, more severe deficits, and PCA or lvPPA versus amnestic AD)

5/n

The negative association between tau-PET and age (younger patients had higher tau-PET burden) was found across phenotypes in a remarkably consistent way
(and very similar to what Whitwell et al found doi.org/10.1016/j.jalz…)

6/n

Looking at the regional information (instead of just extracting global measures), we saw that amyloid-PET patterns were virtually identical across syndromes while tau-PET showed marked differences (w/ common temporo-parietal involvement)

7/n

Tau-PET differences mirrored the differences in brain volume between syndromes (this is a Voxel-Based Morphometry analysis comparing grey matter volumes). This is in line with the strong link described between tau and atrophy (see our recent paper stm.sciencemag.org/content/12/524…)

8/n

We dug a bit more into the correlation between age and tau-PET (described in tweets 5-6). Using voxelwsie analyses, we saw that the association varied across regions and was the strongest in fronto-parietal areas. Temporal lobe tau didn’t seem to vary with age of onset.

9/n

Last set of analyses: APOE! (@ApoEdscvr 🤓).
In this group of amyloid-positive patients with MCI/dementia we found no effect of e4 on global or region amyloid.
But we did find a very focal but very strong effect of e4 on medial temporal tau-PET signal!

10/n

Overall, we found associations between tau patterns and all clinical measures and APOE4.
We didn’t find any association between amyloid and any of the variables…

11/n

One key thing is that older age and APOE4, the two main risk factors for AD, are both associated with a more medial temporal lobe predominant tau pattern (“limbic predominant” per @DrNeuroChic seminal 2011 Lancet Neurology paper doi.org/10.1016/S1474-…)

12/n

This study follows many others, from
- our lab: @RikOssenkoppele’s pubmed.ncbi.nlm.nih.gov/26962052/
- our colleagues @_michael_scholl, @JosephTherr + at @MayoClinic, @biofinder_study, @ucl etc…
- neuropathologists: e.g.@cathrinepet and @grinberg_t ’s pubmed.ncbi.nlm.nih.gov/31250152/

13/n

We also have a lot more to learn from studying the heterogeneity of #Alzheimer’s presentation including sporadic early-onset AD. This is what our lab is currently working on as part of the multi center @LEADS_study with @ApostolovaLiana @DrMariaALZ and @DickersonLabMGH.

14/n

We also need to learn about these atypical variants in a more representative sample of patients. So far, the vast majority of the literature comes from white, educated, and affluent patients. Efforts are ongoing to do a much better job, stay tuned!

15/n

I’ve been very glad to present this data (and a bit more) lately if anyone prefers to listen to a talk:
- at #AAICNN; 10min, recording available to @ISTAART members till dec 10th aaicnn2020.vfairs.com/en/hall
- at the @DouglasResearch; 1h, recording here:

16/n

Thanks to my coauthors, all the patients and caregivers who dedicated times to our study, and our funding sources: @alzassociation (my research fellowship), @NIH (my K99 + Many R and P grants!), @RCFNeuro for the support with our tau-PET program.

17/17