Alzheimer’s disease is the most common type of dementia, reaching 60–80% of case totals, and is one of the major global causes of the elderly population’s decline in functionality concerning daily life activities. Epidemiological research has already indicated that, in addition to several others metabolic factors, diabetes mellitus type 2 is a risk factor of Alzheimer’s disease. Many molecular pathways have been described, and at the same time, there are clues that suggest the connection between type 2 diabetes mellitus and Alzheimer’s disease, through specific genes, autophagy, and even inflammatory pathways. A systematic review with meta-analysis was conducted, and its main goal was to reveal the multilevel connection between these diseases.

Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

Neuropathological and biomarker-based studies indicate that Alzheimer’s disease may sometimes present not with the typical amnestic dementia syndrome of the hippocampal type but with atypical clinical pictures. Atypical presentations include frontal dementia sometimes with additional behavioural component mimicking frontotemporal dementia, logopenic primary progressive aphasia and posterior cortical atrophy, while mixed presentations include patients with additional vascular or Lewy body pathology. More atypical presentations include non-logopenic (semantic, non-fluent agrammatic and unclassifiable) primary progressive aphasia, corticobasal syndrome and cases mixed with normal pressure hydrocephalus. Atypical clinical presentations of Alzheimer’s disease may be more common than previously thought. Cerebrospinal fluid levels of biomarkers such as amyloid beta peptide, hyperphosphorylated tau protein and total tau protein, may offer a useful tool for correct ante mortem identification of such patients, which is likely to affect therapeutic decisions.