THE clinical diagnosis of Alzheimer’s disease (AD) is difficult, especially in early stages of the disease. Today, the diagnosis is based on a typical medical history combined with the exclusion of other causes of dementia. Centers with high specialization can have a diagnostic accuracy of 85% compared with the neuropathological diagnosis. In the early stages of the disease, the clinical picture is vague and definite diagnostic markers have not yet been identified. The development of biochemical diagnostic markers is important for a number of reasons: to support the clinical diagnosis, to allow clinicians to give adequate information to patients and their relatives, to initiate proper pharmacological treatment and care-giving, and to assist in various aspects of clinical research. We have conducted several investigations using material from the Swedish KMAPPNL mutation family and other familial and sporadic AD cases. One theory of later years, the so-called amyloid cascade hypothesis of AD, presumes that Alzheimer pathogenesis is triggered by changes in the metabolism of amyloid precursor protein (APP) and amyloid b-peptide (Ab) (19). It is believed that tangles, containing hyperphosphorylated tau, develop later in the pathological cascade. In our group, the focus of interest are the molecules involved in the pathogenesis of AD: APP, Ab, tau, and apolipoprotein E (apoE 5 protein; APOE 5 gene). We have investigated these markers and their potential as diagnostic instruments in the early stages of the disease. In this work, families with known mutations in the APP and preseniline (PS) genes play an important role, especially the presymptomatic mutation-carriers. To find biological markers for AD in this group represents a tremendous challenge.