The pathology of familial Alzheimer's disease, which is caused by dominant mutations in the gene that encodes amyloid-beta precursor protein (APP) and in those that encode presenilin 1 and presenilin 2, is characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles in multiple brain regions. Here we show that the brain-wide selective disruption of a mutated APP allele in transgenic mouse models carrying the human APP Swedish mutation alleviates amyloid-beta-associated pathologies for at least six months after a single intrahippocampal administration of an adeno-associated virus that encodes both Cas9 and a single-guide RNA that targets the mutation. We also show that the deposition of amyloid-beta, as well as microgliosis, neurite dystrophy and the impairment of cognitive performance, can all be ameliorated when the CRISPR-Cas9 construct is delivered intravenously via a modified adeno-associated virus that can cross the blood-brain barrier. Brain-wide disease-modifying genome editing could represent a viable strategy for the treatment of familial Alzheimer's disease and other monogenic diseases that affect multiple brain regions.
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http://dx.doi.org/10.1038/s41551-021-00759-0 | DOI Listing |
Pharmaceuticals (Basel)
December 2024
Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
A water extract of the Ayurvedic plant (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer's disease and affects dendritic arborization, mitochondrial activity, and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW, although little is known about how interactions between these compounds contribute to the plant's therapeutic benefit.
View Article and Find Full Text PDFSensors (Basel)
January 2025
Physiological Controls Research Center, University Research and Innovation Center, Obuda University, 1034 Budapest, Hungary.
In light of the demographic shift towards an aging population, there is an increasing prevalence of dementia among the elderly. The negative impact on mental health is preventing individuals from taking proper care of themselves. For individuals requiring hospital care, those receiving home care, or as a precaution for a specific individual, it is advantageous to utilize monitoring equipment to track their biological parameters on an ongoing basis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, the envelope protein gene (Human endogenous retroviruses W family envelope protein), located on chromosome 7 and primarily expressed in the human placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well as autoimmune diseases and cancer. Recent studies have highlighted the abnormal expression of cytokines as a key factor in the pathophysiology of schizophrenia.
View Article and Find Full Text PDFBiomolecules
January 2025
School of Systems Biology, George Mason University, Fairfax, VA 22030, USA.
Amylin and amyloid β belong to the same protein family and activate the same receptors. Amyloid β levels are elevated in Alzheimer's disease. Recent studies have demonstrated that amylin-based peptides can reduce the symptoms of Alzheimer's disease in animal models.
View Article and Find Full Text PDFBiomedicines
January 2025
Morpho-Functional Sciences Department, Iuliu Hațieganu University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania.
Despite the massive efforts of modern medicine to stop the evolution of Alzheimer's disease (AD), it affects an increasing number of people, changing individual lives and imposing itself as a burden on families and the health systems. Considering that the vast majority of conventional drug therapies did not lead to the expected results, this review will discuss the newly developing therapies as an alternative in the effort to stop or slow AD. Focused Ultrasound (FUS) and its derived Transcranial Pulse Stimulation (TPS) are non-invasive therapeutic approaches.
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