{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:33:08Z","timestamp":1790836388533,"version":"4.1.0"},"reference-count":92,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,4,19]],"date-time":"2020-04-19T00:00:00Z","timestamp":1587254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Like several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer\u2019s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical \u201cprion-like\u201d manner. Recent genetic studies have identified in four genes associated with inherited AD (amyloid precursor protein-APP, Presenilin-1, Presenilin-2 and Apolipoprotein E), rare mutations which cause dysregulation of APP processing and alterations of folding of the derived amyloid beta peptide (A\u03b2). Accumulation and aggregation of A\u03b2 in the brain can trigger a series of intracellular events, including hyperphosphorylation of tau protein, leading to the pathological features of AD. However, mutations in these four genes account for a small of the total genetic risk for familial AD (FAD). Genome-wide association studies have recently led to the identification of additional AD candidate genes. Here, we review an update of well-established, highly penetrant FAD-causing genes with correlation to the protein misfolding pathway, and novel emerging candidate FAD genes, as well as inherited risk factors. Knowledge of these genes and of their correlated biochemical cascade will provide several potential targets for treatment of AD and aging-related disorders.<\/jats:p>","DOI":"10.3390\/jpm10020026","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T03:23:06Z","timestamp":1587439386000},"page":"26","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["New Insights into the Molecular Bases of Familial Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9273-3698","authenticated-orcid":false,"given":"Valeria","family":"D\u2019Argenio","sequence":"first","affiliation":[{"name":"CEINGE-Biotecnologie Avanzate scarl, via G. Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Human Sciences and Quality of Life Promotion, San Raffaele Open University, via di val Cannuta 247, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-8384","authenticated-orcid":false,"given":"Daniela","family":"Sarnataro","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, Federico II University, via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,19]]},"reference":[{"key":"ref_1","unstructured":"Collaborators GBDD (2019). Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. 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