Dataset for the project "Genetic and epigenetic modulAtors in Rare neurodegenerative diseases with DEmentia: a National study on autosomal dominant Alzheimer disease and genetic frontotemporal degeneration with dementIA (GARDENIA)" European Union—Next Generation EU—NRRP M6C2—Investment 2.1 Enhancement and strengthening of biomedical research in the NHS (PNRR-MR1-2022-12375654) - Cup Code: C83C22001300001

Dataset for the project “Genetic and epigenetic modulAtors in Rare neurodegenerative diseases with DEmentia: a National study on autosomal dominant Alzheimer disease and genetic frontotemporal degeneration with dementIA (GARDENIA)” European Union—Next Generation EU—NRRP M6C2—Investment 2.1 Enhancement and strengthening of biomedical research in the NHS (PNRR-MR1-2022-12375654) - Cup Code: C83C22001300001 PI: Roberta Ghidoni (UO1) UO1) Laboratorio Marcatori Molecolari, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia UO2) SOD Neurologia 1, DAI Neuromuscoloscheletrico e organi di senso, Laboratorio di Neurogenetica - Azienda Ospedaliero Universitaria Careggi, Firenze (Coordinator UO2: Benedetta Nacmias) UO3) Distretto Sanitario di Lamezia Terme, Centro Regionale di Neurogenetica - Azienda Sanitaria Provinciale di Catanzaro (Coordinator UO3: Raffaele Giovanni Maletta) UO4) Dipartimento di Biologia Ecologia e Scienze della Terra, Laboratorio di Genetica - Università della Calabria (Coordinator UO4: Alberto Montesanto) Specific Aim 1 a) to define a harmonized protocol for the collection of clinical and genetic data of patients with rare genetic neurodegenerative diseases with dementia (i.e., autosomal dominant AD and FTD due to a pathogenic mutation); b) to implement institutional biobanks/biorepositories with biological samples of genetic cases; c) to share protocols and best practices established at the Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC); d) to promote the registration of Institutional biorepositories in the Orphanet database to foster research on rare diseases. Specific Aim 2 a) To create a comprehensive core collection of WES and WGM data on a large group of Italian patients/pedigrees with genetic neurodegenerative diseases with dementia (i.e., autosomal dominant AD and FTD due to a pathogenic mutation); b) To identify genetic and epigenetic modifiers of age at onset in genetic neurodegenerative diseases with dementia (i.e., autosomal dominant AD and FTD due to a pathogenic mutation). To this aim we will perform whole exome and whole genome methylation sequencing in Italian patients and pedigrees carrying pathogenic mutations in APP, PSEN1, PSEN2, MAPT, GRN, C9orf72. Specific Aim 3 To validate the gene variants and CpG-sites associated with age at onset as identified in Aim 2b. These associations will be tested in rare forms of neurodegenerative diseases with dementia (i.e., frontotemporal dementia: behavioral variant of frontotemporal dementia, progressive non fluent aphasia). The present dataset contains the following folders: Aim 1a: Protocollo armonizzato_GARDENIA: a folder containing i) CRF GARDENIA.pdf, the case report form created for the collection of clinical and genetic data of patients with rare genetic neurodegenerative diseases with dementia (pdf file) ii) Questionario_Storia_Familiare – GARDENIA.pdf, the family history questionnaire, a form given to families to complete with information about their family history (pdf file). Aim 2a: WES: a folder containing i) GARDENIA.vcf, a file containing all filtered variants (missense, stop-gain, stop-loss, start-loss, indel frameshift) of the subjects identified by WES, with pathogenic mutations and annotations removed ii) Correspondence: a dataset containing sample name (ID sample), sex, Diagnosis, Age at Onset, Genetic group (excel file) WGM: a folder containing i) WGM_ONT, a folder containing raw binary data files generated by Oxforn Nanopore Technology for DNA analyses of presymptomatic subjects AD and FTD patients ii) IDAT_presinto_AD.zip, a raw binary data file generated by Illumina for DNA methylation analyses of presymptomatic subjects and AD patients iii) IDAT_presinto_FTD.zip, a raw binary data file generated by Illumina for DNA methylation analyses of presymptomatic subjects and FTD patients Aim 2b: RawData Gene-Gene interaction: a folder containing i) RawData gene-gene interaction, an excel file of the results included in the article published in IJMS (Int J Mol Sci. 2026 May 2;27(9):4081. doi: 10.3390/ijms27094081) already available in the Zenodo Data Repository at doi: 10.5281/zenodo.18349665 ii) RawData description, a word file with the description of the RawData in the previous excel RawData TMEM106B: a folder containing i) RawData TMEM106B, an excel file of the results included in the article published in Molecular Psychiatry (Mol. Psychiatry. 2026 May 18. doi: 10.1038/s41380-026-03653-w) already available in the Zenodo Data Repository at doi: 10.5281/zenodo.18016695 ii) RawData description, a word file with the description of the RawData in the previous excel Aim 3: Validation_Gardenia: Raw methylation data for the 7 CpG sites significantly associated with onset in 200 FTD patients Users must clarify how they intend to use data here uploaded and whether the research protocol has been approved by an Ethics committee. Data on unpublished results will be available, under the same restrictions, after publication.