Alzheimer's and related dementia research


Agonist –  “is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist, and an inverse agonist causes an action opposite to that of the agonist.”

Alzheimer’s– estimated to account for up to 80 percent of all Dementia cases.  The other major cause of dementia is Vascular Dementia.

Amino Acids –  are used to synthesize proteins and other biomolecules or are oxidized as a source of energy.

Amyloid-beta (Aß) – is formed when Amyloid Precursor Protein (APP) is severed into a shorter chain (a peptide) by two different enzymes (secretase beta and gamma).  The appearance of Aβ occurs many years before the clinical signs and symptoms of the disease.  It is generally accepted that in Alzheimer’s these amyloid beta peptides become misfolded or tangled and form a plague on and in the brain.

Amyloid-beta 40 vs 42 – two possible peptide results from the severing of APP.  Both form plaques in Alzheimer’s.  Aß-40 plaques are less prevalent in those with Lewy bodies (DLB).

ApoE –  Apolipoprotein E is produced primarily by astrocytes, and transports cholesterol (lipid transport) to neurons via ApoE receptors.  ApoE is also involved in lipoprotein metabolism (R) and regulates several important neuronal actions including neuronal repair, synaptogenesis, nerve growth, and development (R).

ApoE 2appears to be neuroprotective.

ApoE 3 – considered the neutral ApoE allele.

ApoE 4 –  the most significant genetic risk factor for onset of Alzheimer’s.  With each ε4 allele the risk of AD increases.

ApoE gene – has three major allelesAPOE-ε2APOE-ε3, and APOE-ε4.  These allelic forms differ by only one or two amino acids , but these differences alter the Apolipoprotein E  structure and function.

ATP – Adenosine triphosphate.  A complex chemical created by our mitochondria and used by our cells for energy.

Autophagy –  A process of recycling cell components back to amino acids for use in cell function and repair.  Autophagy has been demonstrated to improve health and prolong life in various test animals.  Autophagy is triggered by a number of sources including fasting.

Beck Depression Inventory – a 21-question multiple-choice self-report inventory for measuring the severity of depression.  It is one of the most widely used psychometric tests for this purpose.

Cholesterol – (from the Ancient Greek chole- (bile) and stereos (solid), followed by the chemical suffix -ol for an alcohol). It is biosynthesized by all animal cells and is an essential structural component of all animal cell membranes.

Clock Drawing Test –  subjects are asked to draw a clock showing the time (e.g. 10 til 5) and are rated.  “Results indicate that dementia specialists can reliably rate clock drawing test performance using two different qualitative rating approaches. In contrast, the findings do not support the use of the clock drawing test as a standalone screening instrument, as the classification accuracy statistics presented suggest that in mild cognitive impairment, the clinician ratings may be susceptible to both false positive and false negative errors.”

Cytokine – a broad class of proteins involved in the body’s self-defense.  A long list of cytokines are involved in the three phases of immune response 1. Inflammation and attack 2. Anti-inflammatory response and tissue repair and 3. Immunosuppression.

Dementia – a collection of symptoms characterized by the gradual failure to form new memories.   Cognitive functions decline and the sufferer eventually loses the ability to perform even basic day to day functions.

Dysbiosis – the change in the microbiota from balanced to unbalanced (i.e. a reduction in “good” bacteria and an increase in “bad” bacteria).

Energy Homeostasis –  a biological process that regulates food intake (energy inflow) and energy expenditure (energy outflow).  Often out of balance in obesity and type 2 diabetes.  See Leptin and Ghrelin.

Enzyme – An enzyme speeds up a chemical reaction.  Some proteins are enzymes and most enzymes are proteins.

Ferritin – A protein we all produce that binds iron and releases it slowly.  It was used successfully to mute the iron-dependent production of QUIN by 3-HAO.

Framingham Heart Study – Named for the community of Framingham, Massachusetts.  A longitudinal study started in 1948.  Their webpage has a number of health calculators, but the stroke calculator is the most relevant for dementia.

Ghrelin – a hormone produced to tell the brain that the stomach is empty.  Often called the “hunger” hormone.  Ghrelin also plays a significant role in energy homeostasis.

Glycerides – are esters formed from glycerol and fatty acids. Glycerol can be esterified with one, two, or three fatty acids to form monoglyceridesdiglycerides, and triglyceridesVegetable oils and animal fats contain mostly triglycerides, but are broken down by natural enzymes (lipases) into mono and diglycerides and free fatty acids and glycerol.

Glycerol – is a colorless, odorless, sweet-tasting and non-toxic liquid. The glycerol backbone is found in all triglycerides.

Hippocampus – area of the brain critical to learning and memory.  One of the first areas to suffer from neurodegeneration in Alzheimer’s.

IADL – Instrumental Activities of Daily Living let an individual live independently in a community.

Insulin – a hormone produced by the pancreas that regulates glucose levels in the blood.

Insulin Resistance – also Insulin Insensitivity.  A condition where the presence of insulin does not trigger adequate uptake of glucose from the blood.

Leptin – helps to regulate energy homeostasis by inhibiting hunger.  Leptin is opposed by the actions of the hormone ghrelin, the “hunger hormone.”  In obesity, similar to resistance of insulin in type 2 diabetes, a decreased sensitivity to leptin occurs, resulting in an inability to detect satiety despite high energy stores.

Lipid = a biomolecule that does not (or does not easily) dissolve in water.  Specifically fatty acidswaxessterols (including cholesterol), fat-soluble vitamins (such as vitamins A, D, E, and K), monoglyceridesdiglyceridestriglycerides, and phospholipids.

Lipopolysaccharide (LPS)  – LPS is the major component of the outer membrane of Gram-negative bacteria.  LPS can cause systemic inflammation.  It has also been shown to cross the blood brain barrier and combine with Aß plaques.

Lewy bodies (DLB) – very similar to Alzheimer’s, but typically with no family history.

Memory Functioning Questionnaire – typically 64 questions developed to evaluate perception of everyday memory functioning.  The MFQ looks at 4 factors: General Frequency of Forgetting, Seriousness of Forgetting, Retrospective Functioning, and Mnemonics Usage.

Microbiome and Microbiota – the difference between these terms can be a little confusing.  Some researchers use the term “microbiota” to mean the microbes found within a specific environment and the term “microbiome” to mean the collection of microbial genomes in an environment.  However, over time many researchers have started to use these words interchangeably.

Mild Cognitive Impairment (MCI) a pre-dementia condition which often progresses to Alzheimer’s within a few years.

Mitochonria – the plural of mitochondrion and the cellular machinery that cranks out ATP through a multi-stage process.  Our brains are chock full of mitochondria and account for up to 25% of of total oxygen consumption.

MMSE – The Mini–Mental State Examination is used to measure cognitive impairment.  Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10–18 points) or mild (19–23 points) cognitive impairment. (R)  Note – This is not to be confused with mild cognitive impairment (MCI) which is better measured using the MoCA test.  

MoCA – Montreal Cognitive Assessment.  Used to assess mild cognitive impairment.  A one-page 30-point test of cognitive function.  It generally takes about 10 minutes to administer.

Morris Water Test –  a laboratory test of learning and memory using a round tank of water in which the mice or rats look for platforms hidden just under the surface.  The animal gets visual cues so that the next time they are dropped in the water they can get out in a hurry.  Unless of course they can’t remember the last time.

Neurodegeneration  – the progressive loss of neurons through cell death or dysfunction.

Neurogenesis – specifically adult neurogenesis.  The formation of new neurons in the brain.

Novel Object Recognition (NOR) Test – is based on the spontaneous tendency of rodents to spend more time exploring a novel object than a familiar one.  Measures of time spent investigating an object can give insight into the rodent’s memory integrity and attention span.

Parkinson’s Disease – another neurodegenerative disease like Alzheimer’s, but motor skills are effected much earlier and more severely.  Dementia occurs in the later stages of the disease.

Peptide – Amino acids strung together in sequence of generally not more than 50 links.

Probiotic – found in yogurt and other fermented foods.  The World Health Organization’s (WHO) 2001 definition of probiotics is “live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host”.

Protein – Amino acids strung together in sequence numbering generally more than 50 links.

Striatum – coordinates multiple aspects of cognition, including both motor and action planning, decision-making, motivation, reinforcement, and reward perception

Transgenic Mice – genetically modified mice used in research.

Vascular Dementia – dementia caused by stroke.