This research study aims to examine biomarkers of Alzheimer's disease (AD) as early as possible which could potentially be a screening tool for the general population. This observational study will take place at the Skåne University Hospital in Sweden. The study will enroll up to 600 cognitively healthy subjects aged 50 to 80 years with 3/4 having preclinical Alzheimer's disease. Recruitment and enrollment will be ongoing for 2-3 years, and subject participation will be lasting approximately 4 years. Disclosure of AD risk assessments will be an optional procedure.

Inclusion Criteria:

1. Age 50-80

2. Individuals aged 50-60 require at least one of the following risk factors for AD:

   1. Known apolipoprotein E (APOE) -ε4 carrier
   2. Known 1st degree family history of dementia or severe memory loss with onset prior to 75.
   3. Known amyloid brain pathology by either CSF or PET scan.

3. Mini-Mental State Examination (MMSE) ≥26 (aged >65); MMSE ≥27 (aged 50-65).

4. Score of 12 or above on the Montreal Cognitive Assessment (MoCA) telephone version.

5. Speaks and understands Swedish to the extent that an interpreter is not necessary to fully understand the study information and cognitive tests.

6a. Preclinical Alzheimer's disease subgroup (n=450): Amyloid pathology according to cerebrospinal fluid Alzheimer's disease and amyloid PET scans.

6b. Non-Preclinical Alzheimer's disease subgroup (n=150): No sign of preclinical Alzheimer's disease using cerebrospinal fluid Alzheimer's disease biomarkers or Aβ-PET scans.

Exclusion Criteria:

1. Fulfils the criteria for minor or major neurocognitive disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
2. History of significant brain injury or other known neurologic disease or insult, resulting in lasting cognitive sequelae that would confound the assessment and staging of potential neurodegenerative disease.
3. Major depression, bipolar disorder, or recurrent psychotic disorders within the past year.
4. History of alcohol and/or substance abuse or dependence within the past year.
5. Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
6. Refusing or unable to complete baseline cognitive and biomarker assessments (i.e., cognitive testing, blood draw, MRI and PET).

Cognitively unimpaired individuals (50-80 years old) Step 1. Cognitively normal individuals will be screened using plasma p-tau217 (Eli Lilly-developed Meso Scale Discovery method).

Step 2. Cerebrospinal fluid Alzheimer's disease biomarkers analysis will be done in a subpopulation including all plasma p-tau217 positive individuals and randomly selected individuals with normal p-tau217 (matching 9:1).

Step 3. Amyloid PET imaging.

450 individuals with positive Alzheimer's disease biomarkers and 150 with normal Alzheimer's disease biomarkers will be enrolled into longitudinal study.

FOLLOW-UP FOR 4 YEARS: Cognitive testing and blood draws will be conducted at baseline and 12, 24, 36 and 48 months. cerebrospinal fluid collection, MRI, amyloid PET and tau PET will be conducted at baseline, and 24 and 48 months.

Within one year after study completion