Background and Objective: In spinocerebellar ataxia, ataxia onset can be preceded by mild clinical manifestation, cerebellar and/or brainstem alterations or biomarkers modifications. READISCA is a prospective, longitudinal observational study of patients with spinocerebellar ataxias type 1 and 3 to provide essential markers for therapeutic interventions. We looked for clinical, imaging or biological markers that are present at an early-stage of the disease. Methods: We enrolled carriers of a pathological ATXN1 or ATXN3 expansion and controls from 18 US and two European ataxia referral centers. Clinical, cognitive, quantitative motor, neuropsychological measures and plasma neurofilament light chain (NfL) measurements were compared between mutation carriers with and without ataxia and controls. Results: We enrolled 200 participants: 45 carriers of a pathological ATXN1 expansion (31 patients with ataxia (median SARA: 9 [7;10]), 14 mutation carriers without ataxia (1 [0;2])) and 116 carriers of a pathological ATXN3 expansion (80 patients with ataxia (7 [6;9]), 36 mutation carriers without ataxia (1 [0;2])). In addition, we enrolled 39 controls who did not carry a pathological expansion in ATXN1 or ATXN3 . Plasma NfL levels were significantly higher in mutation carriers without ataxia than controls, despite similar mean age (controls: 5.7 pg/mL, SCA1: 18.0 pg/mL (P <0.0001), SCA3: 19.8 pg/mL (P<0.0001). Mutation carriers without ataxia differed from controls by significantly more upper motor signs (SCA1 P=0.0003, SCA3 P=0.003) and by the presence of sensor impairment and diplopia in SCA3 (P=0.0448, and 0.0445 respectively). Functional scales, fatigue and depression scores, swallowing difficulties, and cognitive impairment were worse in mutation carriers with ataxia than those without ataxia. Ataxic SCA3 subjects showed extrapyramidal signs, urinary dysfunction and lower motor neuron signs significantly more often than mutation carriers without ataxia. Discussion: READISCA showed the feasibility of harmonized data acquisition in a multi-national network. NfL alterations, early sensory ataxia and corticospinal signs were quantifiable between preataxic participants and controls. Patients with ataxia differed in many parameters from controls and mutation carriers without ataxia, with a graded increase of abnormal measures from control to preataxic to ataxic cohorts.