Tobias Skillbäck is the first author on a paper about cerebrospinal fluid (CSF) biomarkers for Creutzfeld-Jakob disease (CJD) that we recently published in JAMA Neurology. You can read the abstract here and interviews with Tobias here and here.

CJD is a rare rapidly progressive dementia, which often lead to death within a year from symptom onset. It is characterized by the accumulation of a specific protein, the prion protein. This protein exists normally in the brain, but in the disease it undergoes a conformational change, which makes it harmful to neurons.

Spongiform brain changes (tiny holes where nerve cells have died) in CJD

Previous studies have found that CJD patients have increased CSF levels of the neuronal protein tau, probably reflecting leakage from injured neurons. CSF tau may be increased in other dementias also, for example in Alzheimer's disease. However, in contrast to Alzheimer's disease, CJD does not increase CSF levels of phosphorylated tau. Comparing levels of CSF total tau and phosphorylated tau may therefore be used to differentiate between CJD and other dementias.

The unique approach in Tobias' study was to combine clinical CSF data with information about clinical diagnoses from the Swedish Mortality registry. This identified 9765 deceased individuals with CSF data, 93 of them with CJD as cause-of-death. The project would probably not have been possible to perform in many countries (for example the United States), since it relies on the existence of a unique personal identification number, enabling cross-reference between registries.

We found that these dementia biomarkers have very high diagnostic performance for CJD. This may be useful in clinical settings, to help diagnose this disease. If a treatment is ever developed for CJD, these biomarkers may be part of the algorithm used to determine if a patient with rapidly progressive dementia should receive CJD-specific treatment.

We have just published an article in the journal Brain on the relationship between brain  amyloid-β accumulation, cerebral blood flow and tissue loss. The abstract is available here.

Amyloid-β accumulation is a key feature of Alzheimer's disease, and is known to be related to brain tissue loss, but it is less clear how it is related to functional brain changes, including altered cerebral blood flow. Our paper is called "Association of brain amyloid-β with cerebral perfusion and structure in Alzheimer's disease and mild cognitive impairment". We used PET imaging of brain amyloid-β, combined with MRI measurements of cerebral blood flow and structural volume, in a cohort including both cognitively healthy controls and patients with different degrees of cognitive impairment.

We found that increased brain amyloid-β accumulation is associated with reduced cerebral blood flow, both in cognitively healthy controls, and patients with mild cognitive impairment or Alzheimer's disease with dementia. We also found some indications that high amyloid-β may be associated with greater cerebral blood flow reduction in controls and greater volume reduction in symptomatic disease stages, which is in line with the widely held assumption that amyloid-β accumulation leads to functional brain changes before it leads to structural changes. Naturally, longitudinal studies are needed to verify this.