Persistent olfactory impairment (POI) and dysgeusia are lingering symptoms following recovery from Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. These symptoms, along with neurological changes affecting mood, anxiety, cognitive function, and sleep, have significant public health implications. However, the cause of these symptoms is still unknown. For this reason, we investigated whether the presence of certain proteins, such as amyloid Aβ and α-synuclein in the olfactory mucosa tissue of POI patients, could be associated with neurological changes. We conducted a study where we collected tissue biopsies and cultured cells from patients with normosmic non-cognitive impairment, hyposmic mild cognitive impairment or Alzheimer’s disease, and persistent olfactory impairment (POI) who had been infected with SARS-CoV-2 for 20 months or more. We then examined the expression of amyloid Aβ, α-Synuclein, and tau proteins using immuno-fluorescence and flow cytometry methodology. Our findings revealed that for the first time, amyloid Aβ, α-Synuclein, and tau proteins were detected in olfactory mucosa tissue sections and in cultured olfactory-derived mesenchymal stromal cells from patients with normosmia, hyposmia, and POI post-SARS-CoV-2 with neurological alterations. We also observed that POI occurred in younger post-COVID-19 patients than in those with hyposmia-mild cognitive impairment and normosmia non-cognitive impairment. Immunoreactive positive cells for Aβ, α-syn, and tau proteins were observed in sustentacular-like cells, intermediate cells, and parenchymal sub-lamina propria cells from olfactory mucosa tissue. Our study suggests that the presence of these biomarkers in middle-aged patients may indicate a protein dysmetabolism that could contribute to the progression of a neurodegenerative disorder.