11586 RESULTS
COMMENT The current paper, as well as work from 2021 by Dr. Kanta Horie exploring MTBR-tau243, demonstrates that it is the best fluid biomarker proxy of insoluble tau to date. He has also done fantastic work looking at other forms of MTBR in autosomal-dominant AD
COMMENT This paper has a wealth of data on the 5xFAD and 3xAD Tg models. Overall, it teaches us that manipulation of the peripheral production of specific arachidonic acid-derived oxylipins can ameliorate Alzheimer’s pathology by pleiotropic activities, including
COMMENT This is the third paper that has shown sEH inhibition is beneficial in preventing cognitive decline in Alzheimer’s disease. Importantly, this is the first paper to link sEH in the liver to Alzheimer’s in the brain, though unrelated studies have found conn
COMMENT The significance of this study is that peripherally administered sEH inhibitors may benefit CNS disorders, especially AD, i.e., there’s no need for the drug to cross the blood-brain barrier, which is a major challenge in designing CNS-targeting drugs. The
COMMENT Soluble epoxide hydrolase (sEH) is expressed in both peripheral tissues and CNS. Its upregulation has been implicated in multiple neurological conditions, including depression, Parkinson’s disease, and Alzheimer’s disease. Genetic and pharmacological inhi
COMMENT I fully agree with my colleague Herbert Budka on this very well-written article on the usefulness of brain biopsies—and not only in the context of NPH. In times where AD becomes treatable if the diagnosis is made early, we have to rethink our concerns tak
COMMENT a neurophysiologist at RWTH Aachen Medical School; both are co-authors of this comment
COMMENT These results represent an important step forward to treat AD and offer an encouragement for increasing our efforts in designing new therapeutic strategies against Aβ. Approval by the FDA should be straightforward considering that the deceleration of AD p
COMMENT Amyloid beta oligomers are the accepted neurotoxic agents, while plaque seems to be a protection mechanism. That all of the effective monoclonal antibodies target the oligomers supports the latter's cytotoxic role. Aβ oligomers are cytotoxic at a nan
COMMENT We developed a novel approach to inhibit β-secretase cleavage site of APP by blocking the substrate rather than by inhibiting the total enzymatic activity. This approach overcomes some of the limitations presented by BACE1 inhibition methodologies, as BAC
COMMENT The MBTR of tau represents a hot area of biomarker and drug development. Fluid biomarkers that target N-terminal epitopes (e.g., p-tau181, p-tau217, p-tau231) seem to be better markers for amyloidosis than tau pathology, while tau immunotherapy with N-ter
COMMENT These data are a big step forward toward effective treatment and prevention in AD. Together with results from previous clinically effective and ineffective amyloid-modulating antibodies and low molecular-weight compounds, we should now be positioned to ad
COMMENT It is remarkable that we now have several anti-amyloid therapies that have been proven to slow down the disease progression of Alzheimer’s disease when initiated in amyloid-positive patients with amnestic MCI or mild dementia. While the donanemab Phase 2
COMMENT This work is thrilling and interesting as the authors continue to report deficits of the endo-lysosomal system in aging and neurodegeneration. In both Down's and AD brains, the phosphorylated APP-β-CTF fragment selectively binds to the V0a1 subunit o
COMMENT This is an exciting study implicating the BACE1-generated APP C-terminal fragment as a key player in lysosomal dysfunction in Down’s syndrome fibroblasts and animal models. This work has a major translational implication for the use of BACE inhibitors. Th
